NM_000059.4(BRCA2):c.2490_2491insT (p.Val831fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2022
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:: RCV000774656.13

Allele description [Variation Report for NM_000059.4(BRCA2):c.2490_2491insT (p.Val831fs)]

NM_000059.4(BRCA2):c.2490_2491insT (p.Val831fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2490_2491insT (p.Val831fs)

Other names:

2718_2719insT

HGVS:

NC_000013.11:g.32336845_32336846insT
NG_012772.3:g.26366_26367insT
NM_000059.4:c.2490_2491insTMANE SELECT
NP_000050.2:p.Val831fs
NP_000050.3:p.Val831fs
LRG_293t1:c.2490_2491insT
LRG_293:g.26366_26367insT
LRG_293p1:p.Val831fs
NC_000013.10:g.32910982_32910983insT
NM_000059.3:c.2490_2491insT
p.Val831fs

Protein change:

V831fs

Links:

dbSNP: rs886040430

NCBI 1000 Genomes Browser:

rs886040430

Molecular consequence:

NM_000059.4:c.2490_2491insT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000908535	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29446198, 31300551, 34949660, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000908535

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 31, 2022)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]

PMID:: 29446198
PMCID:: PMC5903938

One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene.

Fostira F, Kostantopoulou I, Apostolou P, Papamentzelopoulou MS, Papadimitriou C, Faliakou E, Christodoulou C, Boukovinas I, Razis E, Tryfonopoulos D, Barbounis V, Vagena A, Vlachos IS, Kalfakakou D, Fountzilas G, Yannoukakos D.

J Med Genet. 2020 Jan;57(1):53-61. doi: 10.1136/jmedgenet-2019-106189. Epub 2019 Jul 12.

PubMed [citation]

PMID:: 31300551
PMCID:: PMC6929701

See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000908535.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 31300551, 34949660) and has been identified in 1 family among the CIMBA participants (PMID: 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as 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: Nov 10, 2024

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