Submissions for variant NM_007294.4(BRCA1):c.213-15A>G

dbSNP: rs886040903

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000258182	SCV000325256	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000521647	SCV000617455	likely pathogenic	not provided	2017-06-08	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.213-15A>G or IVS4-15A>G and consists of an A>G nucleotidesubstitution at the -15 position of intron 4 of the BRCA1 gene. This variant, previously published as BRCA1 332-15A>Gusing alternate nomenclature, has been reported in at least one individual with a family history of breast and ovariancancer (Reitsma 2013). While in silico splicing models are uninformative, transcript analysis reported by Houdayer etal. (2012) revealed BRCA1 c.213-15A>G to use a cryptic site 59 nucleotides upstream of the natural splice site and tohave a severe impact on splicing. BRCA1 c.213-15A>G was not observed in large population cohorts (Lek 2016, The1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). The adenine (A) nucleotide that is altered is notconserved. Based on the currently available information, we consider BRCA1 c.213-15A>G to be a likely pathogenicvariant.
Color Diagnostics, LLC DBA Color Health	RCV000774990	SCV000909083	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855043	SCV002316599	uncertain significance	Hereditary breast ovarian cancer syndrome	2021-05-17	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 22921157, 30078507, 32029870). This variant is also known as 332-15A>G. ClinVar contains an entry for this variant (Variation ID: 267514). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 22505045). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 4 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein.
Intergen, Intergen Genetics and Rare Diseases Diagnosis Center	RCV000258182	SCV005073964	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2024-07-05	criteria provided, single submitter	clinical testing	RNA studies indicate that it may interfere with splicing. (PMID: 22505045)