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:

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


BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • 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
dbSNP: rs369461674
NCBI 1000 Genomes Browser:
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]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
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



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]

Details of each submission

From GeneDx, SCV000535141.4

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


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.

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)


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.

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

Last Updated: Nov 27, 2021

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