NM_033305.3(VPS13A):c.7736_7739del (p.Arg2579fs) AND VPS13A-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 27, 2023
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:: RCV003405407.4

Allele description [Variation Report for NM_033305.3(VPS13A):c.7736_7739del (p.Arg2579fs)]

NM_033305.3(VPS13A):c.7736_7739del (p.Arg2579fs)

Gene:

VPS13A:vacuolar protein sorting 13 homolog A [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

9q21.2

Genomic location:

Preferred name:

NM_033305.3(VPS13A):c.7736_7739del (p.Arg2579fs)

HGVS:

NC_000009.12:g.77356793GA[2]
NG_008931.1:g.184349GA[2]
NM_001018037.2:c.7619_7622del
NM_001018038.3:c.7736_7739del
NM_015186.4:c.7736_7739del
NM_033305.3:c.7736_7739delMANE SELECT
NP_001018047.1:p.Arg2540fs
NP_001018048.1:p.Arg2579fs
NP_056001.1:p.Arg2579fs
NP_150648.2:p.Arg2579fs
NC_000009.11:g.79971708_79971711del
NC_000009.11:g.79971709GA[2]
NM_033305.2:c.7736_7739del
NM_033305.2:c.7736_7739delGAGA

Protein change:

R2540fs

Links:

dbSNP: rs748828128

NCBI 1000 Genomes Browser:

rs748828128

Molecular consequence:

NM_001018037.2:c.7619_7622del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001018038.3:c.7736_7739del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_015186.4:c.7736_7739del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033305.3:c.7736_7739del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: VPS13A-related disorder
Synonyms:: VPS13A-related condition
Identifiers:

Recent activity

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replication protein A 32 kDa subunit isoform X1 [Homo sapiens]
replication protein A 32 kDa subunit isoform X1 [Homo sapiens]
gi|1370454139|ref|XP_024304630.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004113494	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004113494

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 27, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004113494.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The VPS13A c.7736_7739delGAGA variant is predicted to result in a frameshift and premature protein termination (p.Arg2579Asnfs*26). This variant was reported in the compound heterozygous states individuals with choreoacanthocytosis (reported as c.7731_7734delAGAG in Futamura et al 2020. PubMed ID: 32129282; Vaisfeld A et al 2021. PubMed ID: 33652783). This variant is reported in 0.0044% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-79971707-TAGAG-T). Frameshift variants in VPS13A are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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

Last Updated: Sep 29, 2024

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