NM_000059.3(BRCA2):c.631+4A>G AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Likely pathogenic (Last evaluated: May 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001379699.1

Allele description [Variation Report for NM_000059.3(BRCA2):c.631+4A>G]

NM_000059.3(BRCA2):c.631+4A>G

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.631+4A>G
HGVS:
  • NC_000013.11:g.32326617A>G
  • NG_012772.3:g.16138A>G
  • NM_000059.3:c.631+4A>G
  • LRG_293t1:c.631+4A>G
  • LRG_293:g.16138A>G
  • NC_000013.10:g.32900754A>G
Links:
dbSNP: rs397507841
NCBI 1000 Genomes Browser:
rs397507841
Molecular consequence:
  • NM_000059.3:c.631+4A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001577546Invitaecriteria provided, single submitter
Likely pathogenic
(May 13, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway.

Heramb C, Wangensteen T, Grindedal EM, Ariansen SL, Lothe S, Heimdal KR, Mæhle L.

Hered Cancer Clin Pract. 2018;16:3. doi: 10.1186/s13053-017-0085-6.

PubMed [citation]
PMID:
29339979
PMCID:
PMC5761139

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
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001577546.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change falls in intron 7 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 29339979, 29446198). ClinVar contains an entry for this variant (Variation ID: 52056). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20455026, 31143303). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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