VCV000466594.80 - ClinVar

NM_002180.3(IGHMBP2):c.304G>T (p.Ala102Ser)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Likely benign (5)

6 out of 7 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

Variant Details

Identifiers

NM_002180.3(IGHMBP2):c.304G>T (p.Ala102Ser)

Variation ID: 466594 Accession: VCV000466594.80

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.3 11: 68908192 (GRCh38) [ NCBI UCSC ] 11: 68675660 (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	Dec 26, 2017	Jun 20, 2026	Jan 31, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002180.3:c.304G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002171.2:p.Ala102Ser	missense
NC_000011.10:g.68908192G>T
NC_000011.9:g.68675660G>T
NG_007976.1:g.9342G>T
LRG_250:g.9342G>T
LRG_250t1:c.304G>T	LRG_250p1:p.Ala102Ser

... more HGVS ... less HGVS

Protein change

A102S

Other names

Canonical SPDI

NC_000011.10:68908191:G:T

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.

0.00180 (T)

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

Exome Aggregation Consortium (ExAC) 0.00048

The Genome Aggregation Database (gnomAD), exomes 0.00049

1000 Genomes Project 30x 0.00156

The Genome Aggregation Database (gnomAD) 0.00168

1000 Genomes Project 0.00180

The Genome Aggregation Database (gnomAD) 0.00181

Trans-Omics for Precision Medicine (TOPMed) 0.00197

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00216

Links

ClinGen: CA6153255 dbSNP: rs35610053 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.
IGHMBP2		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1462	1548

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.
not provided	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Nov 22, 2023	RCV000712267.43
Autosomal recessive distal spinal muscular atrophy 1 Charcot-Marie-Tooth disease axonal type 2S	Likely benign (1)	criteria provided, single submitter	Jan 31, 2026	RCV001084898.20
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Feb 11, 2020	RCV002448709.9
IGHMBP2-related disorder	Likely benign (1)	no assertion criteria provided	Mar 9, 2020	RCV004553227.2

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.
Likely benign (Dec 22, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not provided	Athena Diagnostics Accession: SCV000842713.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Dec 30, 2019) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000714537.2 First in ClinVar: Apr 09, 2018 Last updated: Sep 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Nov 22, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV004564602.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Feb 11, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV002752916.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (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

Likely benign (Jan 31, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Autosomal recessive distal spinal muscular atrophy 1 Charcot-Marie-Tooth disease axonal type 2S Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000642359.10 First in ClinVar: Dec 26, 2017 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

Uncertain significance (Jul 01, 2022) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV002563074.28 First in ClinVar: Aug 23, 2022 Last updated: Jun 20, 2026	Comment: show IGHMBP2: PM2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely benign (Mar 09, 2020) N Not contributing to aggregate classification	no assertion criteria provided	IGHMBP2-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004737050.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely 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

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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.

Text-mined citations for rs35610053 ...

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 Jun 20, 2026