NM_033305.3(VPS13A):c.9109C>T (p.Arg3037Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 27, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001035586.9

Allele description [Variation Report for NM_033305.3(VPS13A):c.9109C>T (p.Arg3037Ter)]

NM_033305.3(VPS13A):c.9109C>T (p.Arg3037Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9q21.2

Genomic location:

Preferred name:

NM_033305.3(VPS13A):c.9109C>T (p.Arg3037Ter)

HGVS:

NC_000009.12:g.77382007C>T
NG_008931.1:g.209563C>T
NM_001018037.2:c.8992C>T
NM_001018038.3:c.9109C>T
NM_015186.4:c.9109C>T
NM_033305.3:c.9109C>TMANE SELECT
NP_001018047.1:p.Arg2998Ter
NP_001018048.1:p.Arg3037Ter
NP_056001.1:p.Arg3037Ter
NP_150648.2:p.Arg3037Ter
NC_000009.11:g.79996923C>T
NM_033305.2:c.9109C>T

Protein change:

R2998*

Links:

dbSNP: rs199807227

NCBI 1000 Genomes Browser:

rs199807227

Molecular consequence:

NM_001018037.2:c.8992C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001018038.3:c.9109C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015186.4:c.9109C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_033305.3:c.9109C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001198919	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 25, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11381253, 27400454, 12404112, 21598378, 28492532
SCV005332542	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 27, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001198919

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 25, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005332542

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 27, 2024)

germline

clinical testing

Citation Link

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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A conserved sorting-associated protein is mutant in chorea-acanthocytosis.

Rampoldi L, Dobson-Stone C, Rubio JP, Danek A, Chalmers RM, Wood NW, Verellen C, Ferrer X, Malandrini A, Fabrizi GM, Brown R, Vance J, Pericak-Vance M, Rudolf G, Carrè S, Alonso E, Manfredi M, Németh AH, Monaco AP.

Nat Genet. 2001 Jun;28(2):119-20.

PubMed [citation]

PMID:: 11381253

Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.

Mariani LL, Tesson C, Charles P, Cazeneuve C, Hahn V, Youssov K, Freeman L, Grabli D, Roze E, Noël S, Peuvion JN, Bachoud-Levi AC, Brice A, Stevanin G, Durr A.

JAMA Neurol. 2016 Sep 1;73(9):1105-14. doi: 10.1001/jamaneurol.2016.2215.

PubMed [citation]

PMID:: 27400454

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001198919.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 834822). This premature translational stop signal has been observed in individual(s) with VPS13A-related conditions (PMID: 11381253, 21598378, 27400454). This variant is present in population databases (rs199807227, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Arg3037*) in the VPS13A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378).

#	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

From GeneDx, SCV005332542.1

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 21598378, 32439941, 30713892, 11381253, 31345219, 12404112, 36825061, 27400454)

#	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: Oct 26, 2024

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