Submissions for variant NM_000059.4(BRCA2):c.8488-3C>A

dbSNP: rs1566249158

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001351996	SCV001546513	uncertain significance	Hereditary breast ovarian cancer syndrome	2020-03-22	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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 19 of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein, but it affects a nucleotide within the consensus splice site of the intron.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003327509	SCV004034965	uncertain significance	Familial cancer of breast	2023-09-13	criteria provided, single submitter	clinical testing	This sequence change falls in intron area of the BRCA2 gene. It does not directly change the encoded amino acid sequence of the BRCA2 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency).This variant was found in a 35-year-old Korean female patient diagnosed with breast papillary ductal carcinoma with positive family history . Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098).This variant submitted in Clinvar (1047302) by three clinical laboratories and classified as uncertain significant variant . Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
Ambry Genetics	RCV003346508	SCV004052533	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-14	criteria provided, single submitter	clinical testing	The c.8488-3C>A intronic variant results from a C to A substitution 3 nucleotides upstream from coding exon 19 in the BRCA2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355100	SCV001549879	uncertain significance	not provided		no assertion criteria provided	clinical testing
Breast Care Center, Daerim St. Mary`s Hospital	RCV001351996	SCV003935293	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-06-27	no assertion criteria provided	clinical testing	A BRCA2:c.8488-3C>A variant was found in a 35-year-old Korean female patient diagnosed with breast papillary ductal carcinoma. The patient had a family history of breast cancer on her paternal side, with a third-degree relative diagnosed with breast cancer in her 40s. The variant was observed in only one case within the database of a single breast care center institution covering approximately 1700 cases.