NM_000059.4(BRCA2):c.316+1G>A AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 2, 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:: RCV001378664.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.316+1G>A]

NM_000059.4(BRCA2):c.316+1G>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.316+1G>A

HGVS:

NC_000013.11:g.32319326G>A
NG_012772.3:g.8847G>A
NG_017006.2:g.1038C>T
NM_000059.4:c.316+1G>AMANE SELECT
NM_001406719.1:c.316+1G>A
NM_001406720.1:c.316+1G>A
NM_001406721.1:c.316+1G>A
NM_001406722.1:c.-54+1G>A
LRG_293t1:c.316+1G>A
LRG_293:g.8847G>A
NC_000013.10:g.32893463G>A
NM_000059.3:c.316+1G>A

Nucleotide change:

IVS3+1G>A

Links:

dbSNP: rs397507303

NCBI 1000 Genomes Browser:

rs397507303

Molecular consequence:

NM_000059.4:c.316+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.316+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.316+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.316+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.-54+1G>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
SCV001576280	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 2, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 29707112, 32091409, 32641407, 16793542, 20215541, 22194698, 22678057, 24285729, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576280

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 2, 2023)

germline

clinical testing

PubMed (9)
[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

Full in-frame exon 3 skipping of BRCA2 confers high risk of breast and/or ovarian cancer.

Caputo SM, Léone M, Damiola F, Ehlen A, Carreira A, Gaidrat P, Martins A, Brandão RD, Peixoto A, Vega A, Houdayer C, Delnatte C, Bronner M, Muller D, Castera L, Guillaud-Bataille M, Søkilde I, Uhrhammer N, Demontety S, Tubeuf H, Castelain G; French COVAR group collaborators., et al.

Oncotarget. 2018 Apr 3;9(25):17334-17348. doi: 10.18632/oncotarget.24671.

PubMed [citation]

PMID:: 29707112
PMCID:: PMC5915120

Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.

Chen B, Zhang G, Li X, Ren C, Wang Y, Li K, Mok H, Cao L, Wen L, Jia M, Li C, Guo L, Wei G, Lin J, Li Y, Zhang Y, Han-Zhang H, Liu J, Lizaso A, Liao N.

Aging (Albany NY). 2020 Feb 24;12(4):3140-3155. doi: 10.18632/aging.102783. Epub 2020 Feb 24.

PubMed [citation]

PMID:: 32091409
PMCID:: PMC7066887

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576280.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 3 of the BRCA2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 29707112, 32091409). ClinVar contains an entry for this variant (Variation ID: 37822). Studies have shown that disruption of this splice site results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 32641407; Invitae). This variant disrupts a region of the BRCA2 protein in which other variant(s) (p.Trp31Cys) have been determined to be pathogenic (PMID: 16793542, 20215541, 22194698, 22678057, 24285729). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been 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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