NM_007294.3(BRCA1):c.302-5T>C AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 24, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001193803.1

Allele description [Variation Report for NM_007294.3(BRCA1):c.302-5T>C]

NM_007294.3(BRCA1):c.302-5T>C

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.302-5T>C
HGVS:
  • NC_000017.11:g.43104266A>G
  • NG_005905.2:g.113718T>C
  • NM_007294.3:c.302-5T>C
  • NM_007297.4:c.161-5T>C
  • NM_007298.3:c.302-5T>C
  • NM_007299.4:c.302-5T>C
  • NM_007300.4:c.302-5T>C
  • LRG_292t1:c.302-5T>C
  • LRG_292:g.113718T>C
  • NC_000017.10:g.41256283A>G
Links:
dbSNP: rs778668665
NCBI 1000 Genomes Browser:
rs778668665
Molecular consequence:
  • NM_007294.3:c.302-5T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.161-5T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.302-5T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.302-5T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.302-5T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001362921Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 24, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients.

Manguoğlu E, Güran S, Yamaç D, Colak T, Simşek M, Baykara M, Akaydın M, Lüleci G.

Cancer Genet Cytogenet. 2010 Dec;203(2):230-7. doi: 10.1016/j.cancergencyto.2010.07.125.

PubMed [citation]
PMID:
21156238

Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.

Leman R, Gaildrat P, Le Gac G, Ka C, Fichou Y, Audrezet MP, Caux-Moncoutier V, Caputo SM, Boutry-Kryza N, Léone M, Mazoyer S, Bonnet-Dorion F, Sevenet N, Guillaud-Bataille M, Rouleau E, Bressac-de Paillerets B, Wappenschmidt B, Rossing M, Muller D, Bourdon V, Revillon F, Parsons MT, et al.

Nucleic Acids Res. 2018 Sep 6;46(15):7913-7923. doi: 10.1093/nar/gky372. Erratum in: Nucleic Acids Res. 2018 Nov 30;46(21):11656-11657. Nucleic Acids Res. 2020 Feb 20;48(3):1600-1601.

PubMed [citation]
PMID:
29750258
PMCID:
PMC6125621
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362921.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: BRCA1 c.302-5T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant to slightly weaken a 3' acceptor site. However, the variant was shown to have no impact on splicing based on patient mRNA (Leman_2018, Gelli_2019). The variant was absent in 250406 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.302-5T>C has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Manguoglu_2010). This report does not provide an unequivocal conclusion about association of the variant with Hereditary Breast and Ovarian Cancer. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as a VUS - possibly benign variant.

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

Last Updated: Jun 14, 2021

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