ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.932T>A (p.Ile311Asn) (rs145309168)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656967 SCV000149731 uncertain significance not provided 2021-05-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22986143, 26824983, 32019284, 18951446, 28961279, 29263802, 29522266, 29338689, 30111881, 31159747, 31514334, 32255556, 32566746, 33785725, 32068069)
Ambry Genetics RCV000115822 SCV000185850 likely benign Hereditary cancer-predisposing syndrome 2020-04-23 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV000233793 SCV000287734 benign Breast-ovarian cancer, familial 4 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000233793 SCV000488794 uncertain significance Breast-ovarian cancer, familial 4 2016-10-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656967 SCV000602171 likely benign not provided 2019-03-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115822 SCV000686502 likely benign Hereditary cancer-predisposing syndrome 2019-12-11 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115822 SCV000822186 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000709427 SCV000839169 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV000709427 SCV001193724 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000656967 SCV001250268 likely benign not provided 2019-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354391 SCV001548997 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The RAD51D p.Ile311Asn variant was identified in 6 of 1426 proband chromosomes (frequency: 0.0042) from individuals or families with breast and ovarian cancer (Lin 2016, Wickramanayake 2012, Wong 2016). The variant was also identified in dbSNP (ID: rs145309168) as “With Uncertain significance, other allele”, ClinVar (as likely benign by Invitae and as uncertain significance by GeneDx, Ambry Genetics and Counsyl), and Clinvitae databases. The variant was not identified in the Cosmic database. The variant was identified in control databases in 122 of 277230 chromosomes at a frequency of 0.00044 in the following populations: European (Non-Finnish) in 26 of 126716 chromosomes (freq. 0.0002), East Asian in 83 (1 homozygous) of 18868 chromosomes (freq. 0.004), European (Finnish) in 2 of 25794 chromosomes (freq. 0.00008) and South Asian in 9 of 30782 chromosomes (freq. 0.0003), and Other in 2 of 6468 chromosomes (freq. 0.0003), increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant is located in the ATPase domain of the RAD51D protein (Kim 2011). The p.Ile311Asn residue is conserved in mammals but not in more distantly related organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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.

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