NM_007294.4(BRCA1):c.5332+15G>C AND not specified

Clinical significance:Likely benign (Last evaluated: Apr 27, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000423617.3

Allele description [Variation Report for NM_007294.4(BRCA1):c.5332+15G>C]

NM_007294.4(BRCA1):c.5332+15G>C

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5332+15G>C
Other names:
IVS21+15G>C
HGVS:
  • NC_000017.11:g.43051048C>G
  • NG_005905.2:g.166936G>C
  • NM_007294.3:c.5332+15G>C
  • NM_007294.4:c.5332+15G>CMANE SELECT
  • NM_007297.4:c.5191+15G>C
  • NM_007298.3:c.2020+15G>C
  • NM_007299.4:c.2020+15G>C
  • NM_007300.4:c.5395+15G>C
  • LRG_292t1:c.5332+15G>C
  • LRG_292:g.166936G>C
  • NC_000017.10:g.41203065C>G
  • U14680.1:n.5451+15G>C
Links:
Breast Cancer Information Core (BIC) (BRCA1): 5451+15&base_change=G to C; dbSNP: rs80358148
NCBI 1000 Genomes Browser:
rs80358148
Molecular consequence:
  • NM_007294.3:c.5332+15G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.4:c.5332+15G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.5191+15G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.2020+15G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.2020+15G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.5395+15G>C - intron variant - [Sequence Ontology: SO:0001627]
Functional consequence:
functionally_normal [Sequence Ontology: SO:0002219] - Comment(s)

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
SCV000512321GeneDxcriteria provided, single submitter
Likely benign
(Sep 7, 2017)
germlineclinical testing

Citation Link,

SCV000699237Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Apr 27, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Assessing the RNA effect of 26 DNA variants in the BRCA1 and BRCA2 genes.

Menéndez M, Castellsagué J, Mirete M, Pros E, Feliubadaló L, Osorio A, Calaf M, Tornero E, del Valle J, Fernández-Rodríguez J, Quiles F, Salinas M, Velasco A, Teulé A, Brunet J, Blanco I, Capellá G, Lázaro C.

Breast Cancer Res Treat. 2012 Apr;132(3):979-92. doi: 10.1007/s10549-011-1661-5. Epub 2011 Jul 7.

PubMed [citation]
PMID:
21735045

Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: inter-reviewer variability and promotion of minimum reporting guidelines.

Walker LC, Whiley PJ, Houdayer C, Hansen TV, Vega A, Santamarina M, Blanco A, Fachal L, Southey MC, Lafferty A, Colombo M, De Vecchi G, Radice P, Spurdle AB; ENIGMA consortium..

Hum Mutat. 2013 Oct;34(10):1424-31. doi: 10.1002/humu.22388. Epub 2013 Aug 13.

PubMed [citation]
PMID:
23893897

Details of each submission

From GeneDx, SCV000512321.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699237.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: BRCA1 c.5332+15G>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. 4/4 computational tools predict no significant impact on normal splicing. The variant allele was found at a frequency of 1.6e-05 in 251236 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5332+15G>C in individuals affected with Hereditary Breast and Ovarian Cancer has been reported in the peer-reviewed literature. However, at-least one database (BIC) listed this variant as found in affected patient diagnosed with breast cancer at 53 and in unaffected duaghter". At least one publication reports experimental evidence evaluating an impact on splicing. These results showed no damaging effect of this variant on splicing that have also been further corroborated by other studies reporting no impact on homology directed repair (primary evidence unavailable). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 10, 2021

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