Submissions for variant NM_002878.4(RAD51D):c.39C>G (p.Thr13=)

gnomAD frequency: 0.00018  dbSNP: rs146448657

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164140	SCV000214756	likely benign	Hereditary cancer-predisposing syndrome	2014-09-02	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000989840	SCV000287710	likely benign	Breast-ovarian cancer, familial, susceptibility to, 4	2025-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000589703	SCV000514353	likely benign	not provided	2020-06-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164140	SCV000691337	likely benign	Hereditary cancer-predisposing syndrome	2015-10-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589703	SCV000698101	likely benign	not provided	2016-10-28	criteria provided, single submitter	clinical testing	Variant summary: The RAD51D c.39C>G (p.Thr13Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 9/119710 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0008858 (9/10160). This frequency is about 7 times the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as probably benign until more information becomes available.
Mendelics	RCV000989840	SCV001140430	likely benign	Breast-ovarian cancer, familial, susceptibility to, 4	2019-05-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164140	SCV002534814	likely benign	Hereditary cancer-predisposing syndrome	2021-05-19	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003895124	SCV004712722	likely benign	RAD51D-related disorder	2020-08-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).