NM_001001331.4(ATP2B2):c.1891G>A (p.Val631Met) AND Agenesis of the corpus callosum with peripheral neuropathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Benign (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001258253.1

Allele description

NM_001001331.4(ATP2B2):c.1891G>A (p.Val631Met)

Gene:

ATP2B2:ATPase plasma membrane Ca2+ transporting 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_001001331.4(ATP2B2):c.1891G>A (p.Val631Met)

HGVS:

NC_000003.12:g.10359892C>T
NG_012046.2:g.353140G>A
NM_001001331.4:c.1891G>AMANE SELECT
NM_001330611.3:c.1756G>A
NM_001353564.1:c.1756G>A
NM_001363862.1:c.1756G>A
NM_001683.5:c.1756G>A
NP_001001331.1:p.Val631Met
NP_001317540.1:p.Val586Met
NP_001340493.1:p.Val586Met
NP_001350791.1:p.Val586Met
NP_001674.2:p.Val586Met
NC_000003.11:g.10401576C>T
NM_001683.3:c.1756G>A

Protein change:

V586M; VAL586MET

Links:

OMIM: 108733.0001; dbSNP: rs61736451

NCBI 1000 Genomes Browser:

rs61736451

Molecular consequence:

NM_001001331.4:c.1891G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330611.3:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353564.1:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363862.1:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001683.5:c.1756G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Agenesis of the corpus callosum with peripheral neuropathy (ACCPN)
Synonyms:: Andermann syndrome; Charlevoix disease; Corpus callosum agenesis neuronopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0000902; MedGen: C0795950; Orphanet: 1496; OMIM: 218000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001435167	Broad Institute Rare Disease Group, Broad Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	research	PubMed (3) [See all records that cite these PMIDs] 15829536, 22047666, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001435167

Broad Institute Rare Disease Group, Broad Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

research

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Modification of human hearing loss by plasma-membrane calcium pump PMCA2.

Schultz JM, Yang Y, Caride AJ, Filoteo AG, Penheiter AR, Lagziel A, Morell RJ, Mohiddin SA, Fananapazir L, Madeo AC, Penniston JT, Griffith AJ.

N Engl J Med. 2005 Apr 14;352(15):1557-64. Erratum in: N Engl J Med. 2005 Jun 2;352(22):2362.

PubMed [citation]

PMID:: 15829536

Mutations in PMCA2 and hereditary deafness: a molecular analysis of the pump defect.

Giacomello M, De Mario A, Lopreiato R, Primerano S, Campeol M, Brini M, Carafoli E.

Cell Calcium. 2011 Dec;50(6):569-76. doi: 10.1016/j.ceca.2011.09.004. Epub 2011 Nov 1.

PubMed [citation]

PMID:: 22047666

See all PubMed Citations (3)

Details of each submission

From Broad Institute Rare Disease Group, Broad Institute, SCV001435167.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (3)

Description

The heterozygous p.Val586Met variant, sometimes called p.Val631Met due to a difference in cDNA numbering, in ATP2B2 has been identified in at least 5 individuals with hearing loss, including 3 siblings from 1 family (PMID: 15829536). Of note, 2 additional siblings in the same family did not have this variant and are less severely affected by disease. All 5 siblings were reported to be homozygous for a separate, causal variant in CDH23 (PMID: 15829536). This variant has also been identified in >4% of Latino chromosomes and 22 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Val586Met variant may have a mild impact on protein function (PMID: 22047666). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal recessive deafness but may modify disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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