Submissions for variant NM_002878.4(RAD51D):c.33C>T (p.Gly11=)

dbSNP: rs760444811

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000217335	SCV000275597	likely benign	Hereditary cancer-predisposing syndrome	2015-05-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000217335	SCV000906717	likely benign	Hereditary cancer-predisposing syndrome	2017-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001477316	SCV001681551	likely benign	Breast-ovarian cancer, familial, susceptibility to, 4	2025-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000649722	SCV001863695	likely benign	not provided	2019-07-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000217335	SCV002534797	likely benign	Hereditary cancer-predisposing syndrome	2021-09-05	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267959	SCV002550934	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355007	SCV001549760	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The RAD51D p.Gly11= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs760444811) as "With Likely benign allele", ClinVar (classified as likely benign by Invitae and Ambry Genetics). The variant was identified in control databases in 3 of 242614 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 3 of 109352 chromosomes (freq: 0.00003), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The c.33C>T variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing, one predicting a the gain of a 5’ splicing site and one predicting the gain of a 3’ splice site; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.