NM_000059.4(BRCA2):c.67+2T>A AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 9, 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:: RCV003529937.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.67+2T>A]

NM_000059.4(BRCA2):c.67+2T>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.67+2T>A

Other names:

IVS2+2T>A

HGVS:

NC_000013.11:g.32316529T>A
NG_012772.3:g.6050T>A
NG_017006.2:g.3835A>T
NM_000059.4:c.67+2T>AMANE SELECT
NM_001406719.1:c.67+2T>A
NM_001406720.1:c.67+2T>A
NM_001406721.1:c.67+2T>A
NM_001406722.1:c.-303+862T>A
LRG_293t1:c.67+2T>A
LRG_293:g.6050T>A
NC_000013.10:g.32890666T>A
NM_000059.3:c.67+2T>A
U43746.1:n.295+2T>A

Links:

Breast Cancer Information Core (BIC) (BRCA2): 295+2&base_change=T to A; dbSNP: rs81002885

NCBI 1000 Genomes Browser:

rs81002885

Molecular consequence:

NM_001406722.1:c.-303+862T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000059.4:c.67+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.67+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.67+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.67+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295468	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 9, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17011978, 22505045, 18092194, 21063910, 31742824, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295468

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 9, 2023)

germline

clinical testing

PubMed (6)
[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

RNA-based analysis of BRCA1 and BRCA2 gene alterations.

Bonatti F, Pepe C, Tancredi M, Lombardi G, Aretini P, Sensi E, Falaschi E, Cipollini G, Bevilacqua G, Caligo MA.

Cancer Genet Cytogenet. 2006 Oct 15;170(2):93-101.

PubMed [citation]

PMID:: 17011978

Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.

Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, et al.

Hum Mutat. 2012 Aug;33(8):1228-38. doi: 10.1002/humu.22101. Epub 2012 May 11.

PubMed [citation]

PMID:: 22505045

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295468.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 2 and introduces a premature termination codon (PMID: 17011978, 22505045). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 52162). This variant is also known as IVS2+2T>A. Disruption of this splice site has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 18092194, 21063910, 31742824). It has also been observed to segregate with disease in related individuals. This sequence change affects a donor splice site in intron 2 of the BRCA2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.

#	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 3, 2024

ClinVar

Relating variation to medicine