NM_007294.4(BRCA1):c.212+17T>C AND not specified

Clinical significance:Likely benign (Last evaluated: May 17, 2021)

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:
RCV000423045.2

Allele description [Variation Report for NM_007294.4(BRCA1):c.212+17T>C]

NM_007294.4(BRCA1):c.212+17T>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.212+17T>C
HGVS:
  • NC_000017.11:g.43106439A>G
  • NG_005905.2:g.111545T>C
  • NM_007294.4:c.212+17T>CMANE SELECT
  • NM_007297.4:c.71+17T>C
  • NM_007298.3:c.212+17T>C
  • NM_007299.4:c.212+17T>C
  • NM_007300.4:c.212+17T>C
  • LRG_292t1:c.212+17T>C
  • LRG_292:g.111545T>C
  • NC_000017.10:g.41258456A>G
  • NM_007294.3:c.212+17T>C
Links:
dbSNP: rs369461674
NCBI 1000 Genomes Browser:
rs369461674
Molecular consequence:
  • NM_007294.4:c.212+17T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.71+17T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.212+17T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.212+17T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.212+17T>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
SCV000535141GeneDxcriteria provided, single submitter
Likely benign
(Dec 15, 2016)
germlineclinical testing

Citation Link,

SCV001623159Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(May 17, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

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

Incorporation of semi-quantitative analysis of splicing alterations for the clinical interpretation of variants in BRCA1 and BRCA2 genes.

Montalban G, Bonache S, Moles-Fernández A, Gadea N, Tenés A, Torres-Esquius S, Carrasco E, Balmaña J, Diez O, Gutiérrez-Enríquez S.

Hum Mutat. 2019 Dec;40(12):2296-2317. doi: 10.1002/humu.23882. Epub 2019 Aug 26.

PubMed [citation]
PMID:
31343793

Details of each submission

From GeneDx, SCV000535141.4

#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, SCV001623159.1

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

Description

Variant summary: BRCA1 c.212+17T>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. A recently published study evaluating splicing impact using semi-quantitative capillary electrophoresis, Sanger sequencing and allele-specific assays did not detect any abnormal transcripts indicative of no impact on splicing. This variant was classified as benign (Class 1 variant) following the ENIGMA guidelines (Montalban_2019). The variant was absent in 247566 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.212+17T>C has been reported in the literature in at-least one individual affected with stomach cancer who had a family history of various cancers (Montalban_2019). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Four 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 benign (n=1)/likely benign (n=3). 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 27, 2021

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