Submissions for variant NM_007294.4(BRCA1):c.212+5A>G

dbSNP: rs2054767462

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001072655	SCV001285183	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2018-03-30	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001364320	SCV001560460	uncertain significance	Hereditary breast ovarian cancer syndrome	2021-07-16	criteria provided, single submitter	clinical testing	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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant does not affect mRNA splicing (PMID: 30209399). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 865268). 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, but it affects a nucleotide within the consensus splice site of the intron.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005394727	SCV006058309	uncertain significance	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Fanconi anemia, complementation group S	2022-11-16	criteria provided, single submitter	clinical testing
Brotman Baty Institute, University of Washington	RCV001072655	SCV001238077	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro