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NM_177438.2(DICER1):c.1124C>G (p.Pro375Arg)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(2);Likely benign(2);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Aug 30, 2021)
Last evaluated:
Dec 2, 2020
Accession:
VCV000242032.12
Variation ID:
242032
Description:
single nucleotide variant
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NM_177438.2(DICER1):c.1124C>G (p.Pro375Arg)

Allele ID
241997
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q32.13
Genomic location
14: 95124448 (GRCh38) GRCh38 UCSC
14: 95590785 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_492t1:c.1124C>G LRG_492p1:p.Pro375Arg
NC_000014.8:g.95590785G>C
NC_000014.9:g.95124448G>C
... more HGVS
Protein change
P375R
Other names
-
Canonical SPDI
NC_000014.9:95124447:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (C)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00019
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00025
The Genome Aggregation Database (gnomAD), exomes 0.00035
Exome Aggregation Consortium (ExAC) 0.00035
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
Links
ClinGen: CA7331526
dbSNP: rs148758903
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign/Likely benign 3 criteria provided, multiple submitters, no conflicts Dec 2, 2020 RCV000231396.10
Uncertain significance 1 criteria provided, single submitter Oct 14, 2018 RCV000570796.1
Benign 1 criteria provided, single submitter Jul 1, 2019 RCV001201043.2
Uncertain significance 1 criteria provided, single submitter Apr 10, 2020 RCV001292801.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DICER1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3396 3417

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Benign
(Jan 12, 2018)
criteria provided, single submitter
Method: clinical testing
DICER1-related pleuropulmonary blastoma cancer predisposition syndrome
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000389766.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
Likely benign
(Dec 02, 2020)
criteria provided, single submitter
Method: clinical testing
DICER1-related pleuropulmonary blastoma cancer predisposition syndrome
Allele origin: germline
Invitae
Accession: SCV000291603.8
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Oct 14, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000661811.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.P375R variant (also known as c.1124C>G), located in coding exon 7 of the DICER1 gene, results from a C to G substitution at nucleotide … (more)
Likely benign
(Oct 07, 2020)
criteria provided, single submitter
Method: clinical testing
DICER1-related pleuropulmonary blastoma cancer predisposition syndrome
Allele origin: germline
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital
Accession: SCV000891032.2
Submitted: (Dec 15, 2020)
Evidence details
Comment:
The DICER1 c.1124C>G (p.Pro375Arg) missense change has a maximum subpopulation frequency of 0.05% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/14-95590785-G-C). This population frequency is higher than expected for … (more)
Uncertain significance
(Apr 10, 2020)
criteria provided, single submitter
Method: clinical testing
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors
Allele origin: paternal
Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481455.2
Submitted: (Feb 10, 2021)
Evidence details
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Benign
(Jul 01, 2019)
criteria provided, single submitter
Method: curation
Not Specified
Allele origin: germline
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Accession: SCV001372045.2
Submitted: (Aug 30, 2021)
Evidence details
Publications
PubMed (1)
Comment:
ACMG criteria met: PP5, BS1, BS2, BP1

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma. Wasserman JD The Journal of clinical endocrinology and metabolism 2018 PMID: 29474644
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532

Text-mined citations for rs148758903...

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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 Sep 07, 2021