VCV000801893.16 - ClinVar

NM_004044.7(ATIC):c.347C>G (p.Thr116Ser)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign
Benign (4)

4 out of 15 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Functional data are available for this variant

Variant Details

Identifiers

NM_004044.7(ATIC):c.347C>G (p.Thr116Ser)

Variation ID: 801893 Accession: VCV000801893.16

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q35 2: 215325297 (GRCh38) [ NCBI UCSC ] 2: 216190020 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 11, 2020	Feb 23, 2026	Feb 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_004044.7:c.347C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004035.2:p.Thr116Ser	missense
NM_004044.6:c.347C>G
NC_000002.12:g.215325297C>G
NC_000002.11:g.216190020C>G
NG_013002.1:g.18342C>G

... more HGVS ... less HGVS

Protein change

T116S

Other names

Canonical SPDI

NC_000002.12:215325296:C:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.27776 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.25724

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.24681

Exome Aggregation Consortium (ExAC) 0.32347

The Genome Aggregation Database (gnomAD), exomes 0.32522

The Genome Aggregation Database (gnomAD), exomes 0.32548

1000 Genomes Project 30x 0.26983

The Genome Aggregation Database (gnomAD) 0.24863

Trans-Omics for Precision Medicine (TOPMed) 0.25251

1000 Genomes Project 0.27776

Links

ClinGen: CA2092922 dbSNP: rs2372536 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATIC		-	-	GRCh38 GRCh37	199	414

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
AICA-ribosiduria	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 14, 2021	RCV000987027.4
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2026	RCV002067574.8
ATIC-related disorder	Benign (1)	no assertion criteria provided	Oct 18, 2019	RCV003972998.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (May 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	AICA-ribosiduria	Mendelics Accession: SCV001136208.1 First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005243819.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Jul 14, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	AICA-ribosiduria	Genome-Nilou Lab Accession: SCV001775036.2 First in ClinVar: Aug 13, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Feb 01, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002414636.5 First in ClinVar: Apr 12, 2022 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Oct 18, 2019) N Not contributing to aggregate classification	no assertion criteria provided	ATIC-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004797493.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Submissions - Functional Data

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0002),junction spanning - intron inclusion with mutation (p=0.0),read abundance - intron inclusion (p=0.0059)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (50 reads, p=0.0002), junction spanning - intron inclusion with mutation (50 reads, p=0.0), read abundance - intron inclusion (16 reads, p=0.0059). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049188.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FF-A7CQ), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-FF-A7CQ
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion with mutation (p=0.004),read abundance - intron inclusion (p=0.0059)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion with mutation (20 reads, p=0.004), read abundance - intron inclusion (16 reads, p=0.0059). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049190.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GS-A9TV), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-GS-A9TV
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion with mutation (p=0.0231)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion with mutation (14 reads, p=0.0231). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049191.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GS-A9TZ), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-GS-A9TZ
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0342),junction spanning - intron inclusion with mutation (p=0.0305)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (25 reads, p=0.0342), junction spanning - intron inclusion with mutation (13 reads, p=0.0305). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049192.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GS-A9U4), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-GS-A9U4
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0128),junction spanning - intron inclusion with mutation (p=0.003)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (30 reads, p=0.0128), junction spanning - intron inclusion with mutation (21 reads, p=0.003). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049193.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FA-A4XK), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-FA-A4XK
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion with mutation (p=0.0073)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion with mutation (18 reads, p=0.0073). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049194.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FA-A82F), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-FA-A82F
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion with mutation (p=0.0305),read abundance - intron inclusion (p=0.0016)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion with mutation (13 reads, p=0.0305), read abundance - intron inclusion (19 reads, p=0.0016). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049195.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FA-A7DS), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-FA-A7DS
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0045),junction spanning - intron inclusion with mutation (p=0.0016),read abundance - intron inclusion (p=0.0448)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (35 reads, p=0.0045), junction spanning - intron inclusion with mutation (23 reads, p=0.0016), read abundance - intron inclusion (11 reads, p=0.0448). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049196.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-FF-A7CR), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-FF-A7CR
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0233),junction spanning - intron inclusion with mutation (p=0.0005),read abundance - intron inclusion (p=0.0206)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (27 reads, p=0.0233), junction spanning - intron inclusion with mutation (27 reads, p=0.0005), read abundance - intron inclusion (13 reads, p=0.0206). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049197.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GR-A4D4), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-GR-A4D4
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

functionally abnormal -- retained intron

assessed by RNAseq

Result:

junction spanning - intron inclusion (p=0.0128),junction spanning - intron inclusion with mutation (p=0.0002),read abundance - intron inclusion (p=0.0137)

Modifies an exonic cryptic donor site at NC_000002.11:g.216190016 from 0.83 to 4.70 bits. Significant p-values: junction spanning - intron inclusion (30 reads, p=0.0128), junction spanning - intron inclusion with mutation (30 reads, p=0.0002), read abundance - intron inclusion (14 reads, p=0.0137). Computations were originally performed using genomic coordinates. This variant was mapped to an appropriate current MANE database designation or, if not present in this source, to the longest relevant transcript in the Biocommons Universal Transcript Archive using the hgvs Python package. The original genomic coordinate was based on GRCh37 and was submitted as an "Alternate designation". Modifications of Figure 2 of PMID:31275557 for ClinVar: a) "strongly corroborating Veridical p-value" refers to "junction-spanning" evidence types; b) add the text "and natural site < 300 nucleotides away?" to "Ri,final > nearest natural site Ri"; c) "Aberrant" and "Likely aberrant" classifications are now both defined as "Functionally abnormal" (analogous to ACMG/AMP reporting); d) "Allele-specific alternative splicing" classification now defined as "Function uncertain" (based on results for similar variants in PMID: 32211018); e) average heterozygosity based-criteria no longer contribute to classification.

Citation: PubMed: 31275557

Dr. Peter K. Rogan Lab, Western University

Accession: SCV007049198.1

Submitted: 2025-10-17

Assay description:

In the sample (TCGA-GR-A4D5), the counts of splice junction spanning reads and abundance of the transcript adjacent to this mutation were compared with RNASeq data from matched tissues and tumors lacking the same mutation using Veridical (PMID:24741438)

Disease context: Malignant lymphoma, large B-cell, diffuse
Transcript, protein change: NM_004044.7:c.347C>G, T116S
Molecular phenotype measured: splicing
Cell line: TCGA-GR-A4D5
Tissue: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC)
Collection method: in vitro
Species: human
Number of controls: 127

Text-mined citations for rs2372536 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Mar 01, 2026