Submissions for variant NM_000059.4(BRCA2):c.7618-16T>G

dbSNP: rs397507924

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084315	SCV000073277	likely benign	Hereditary breast ovarian cancer syndrome	2023-11-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000235946	SCV000293935	uncertain significance	not provided	2016-02-09	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.7618-16T>G or IVS15-16T>G and consists of a T>G nucleotide substitution at the -16 position of intron 15 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 7846-16T>G. Multiple in silico models predict this variant to weaken the nearby natural acceptor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 c.7618-16T>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The thymine (T) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether BRCA2 c.7618-16T>G is pathogenic or benign.
Color Diagnostics, LLC DBA Color Health	RCV000771917	SCV000904697	likely benign	Hereditary cancer-predisposing syndrome	2015-04-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781058	SCV000918849	uncertain significance	not specified	2018-06-01	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.7618-16T>G 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. Several computational tools predict a significant impact on normal splicing: one predicts that the variant abolishes a 3 prime acceptor site, and two predict the weakening of the 3 prime acceptor site. An in silico study also predicted that the variant of interest weakens a natural splicing site (Mucaki 2011). However, these predictions have yet to be confirmed by functional studies. The variant was absent in 243754 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7618-16T>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV005007974	SCV005633970	uncertain significance	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer	2024-06-20	criteria provided, single submitter	clinical testing