NM_014231.5(VAMP1):c.340+2T>G AND not provided

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 3, 2023
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:: RCV000255544.5

Allele description

NM_014231.5(VAMP1):c.340+2T>G

Genes:

TAPBPL:TAP binding protein like [Gene - OMIM - HGNC]
VAMP1:vesicle associated membrane protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_014231.5(VAMP1):c.340+2T>G

HGVS:

NC_000012.12:g.6464888A>C
NG_042188.2:g.11012T>G
NM_001297438.2:c.340+2T>G
NM_014231.5:c.340+2T>GMANE SELECT
NM_016830.4:c.340+2T>G
NM_199245.3:c.342T>G
NP_954740.1:p.Ser114Arg
NC_000012.11:g.6574054A>C
NM_014231.3:c.340+2T>G

Nucleotide change:

IVS4AS, T-G, +2

Protein change:

S114R

Links:

OMIM: 185880.0001; dbSNP: rs878854975

NCBI 1000 Genomes Browser:

rs878854975

Molecular consequence:

NM_199245.3:c.342T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001297438.2:c.340+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_014231.5:c.340+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_016830.4:c.340+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000322101	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 3, 2023)	germline	clinical testing	Citation Link,
SCV000844856	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Nov 30, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22958904, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000322101

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 3, 2023)

germline

clinical testing

Citation Link,

SCV000844856

Athena Diagnostics Inc

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Nov 30, 2017)

germline

clinical testing

PubMed (2)
[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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.

Bourassa CV, Meijer IA, Merner ND, Grewal KK, Stefanelli MG, Hodgkinson K, Ives EJ, Pryse-Phillips W, Jog M, Boycott K, Grimes DA, Goobie S, Leckey R, Dion PA, Rouleau GA.

Am J Hum Genet. 2012 Sep 7;91(3):548-52. doi: 10.1016/j.ajhg.2012.07.018.

PubMed [citation]

PMID:: 22958904
PMCID:: PMC3511983

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000322101.9

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

Description

Published functional studies demonstrate that this variant affects a critical donor site for the splicing of VAMP1 isoforms and results in an in-frame addition of 33 amino acids (Bourassa et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22958904, 27957547, 11774073)

#	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

From Athena Diagnostics Inc, SCV000844856.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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: Feb 14, 2024

ClinVar

Relating variation to medicine