ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.568G>A (p.Ala190Thr) (rs80116829)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000586998 SCV000149727 likely benign not provided 2020-09-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26261251, 25980754, 27443514, 27878467, 25186627)
Ambry Genetics RCV000115818 SCV000185251 likely benign Hereditary cancer-predisposing syndrome 2018-10-02 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000586998 SCV000231658 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing
Invitae RCV000205150 SCV000262323 benign Breast-ovarian cancer, familial 4 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000205150 SCV000488990 uncertain significance Breast-ovarian cancer, familial 4 2016-07-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586998 SCV000602162 likely benign not provided 2019-12-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586998 SCV000698108 benign not provided 2016-02-15 criteria provided, single submitter clinical testing
Mendelics RCV000709438 SCV000839181 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115818 SCV000910663 benign Hereditary cancer-predisposing syndrome 2015-11-04 criteria provided, single submitter clinical testing
Mendelics RCV000205150 SCV001140414 uncertain significance Breast-ovarian cancer, familial 4 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000205150 SCV001474061 likely benign Breast-ovarian cancer, familial 4 2020-03-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354077 SCV001548604 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The RAD51D p.Ala190Thr variant was identified in 4 of 9622 proband chromosomes (frequency: 0.0004) from individuals or families with ovarian cancer, breast cancer, or Lynch syndrome and was not identified in 5544 control chromosomes from healthy individuals (Song 2015, Yadav 2017, Yurgelun 2015). The variant was also identified in dbSNP (ID: rs80116829 as "With other allele") and ClinVar (2x as benign by Invitae and Integrated Genetics/Laboratory Corporation of America; 2x as likely benign by GeneDx and Ambry Genetics; and 3x as uncertain significance by Counsyl, EGL Genetic Diagnostics, and Quest Diagnostics Nichols Institute). The variant was not identified in Cosmic. The variant was identified in control databases in 135 of 274972 chromosomes at a frequency of 0.0005, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 126 of 23588 chromosomes (freq: 0.005), Other in 1 of 6420 chromosomes (freq: 0.0002), Latino in 6 of 34238 chromosomes (freq: 0.0002), European in 1 of 125754 chromosomes (freq: 0.000008), and South Asian in 1 of 30414 chromosomes (freq: 0.00003), while the variant was not observed in the Ashkenazi Jewish, East Asian, or Finnish populations. The p.Ala190 residue is not conserved in mammals and 5 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and only 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.