ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.1875C>G (p.Tyr625Ter) (rs149201802)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205188 SCV000261499 pathogenic Hereditary cancer-predisposing syndrome 2020-10-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr625*) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs149201802, ExAC 0.08%). This variant has been reported in the literature in individuals affected with pancreatic and breast cancer (PMID: 18281469, 25452441). ClinVar contains an entry for this variant (Variation ID: 220719). Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520, 16385572). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000205188 SCV000273485 pathogenic Hereditary cancer-predisposing syndrome 2018-07-03 criteria provided, single submitter clinical testing The p.Y625* pathogenic mutation (also known as c.1875C>G), located in coding exon 12 of the RAD50 gene, results from a C to G substitution at nucleotide position 1875. This changes the amino acid from a tyrosine to a stop codon within coding exon 12. This pathogenic mutation was previously reported in a male diagnosed with pancreatic cancer (Wang X et al. Cancer Res. 2008 Feb;68:971-5). This mutation was also observed two times among 1824 triple negative breast cancer patients unselected for family history (Couch FJ et al. J. Clin. Oncol. 2015 Feb;33:304-11). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Counsyl RCV000411352 SCV000489273 pathogenic Nijmegen breakage syndrome-like disorder 2016-09-13 criteria provided, single submitter clinical testing
GeneKor MSA RCV000205188 SCV000821772 pathogenic Hereditary cancer-predisposing syndrome 2020-01-01 criteria provided, single submitter clinical testing This variant is a single amino acid change from Tytosine to a premature translational stop signal at codon 625 of the RAD50 protein. This is expected to result in an absent or disrupted protein product. Truncating variants in RAD50 are known to be pathogenic (PMID: 19409520, 16385572).This variant has been described in the international literature in individuals affected with pancreatic and breast cancer (PMID: 18281469, 25452441) and in individuals undergoing panel testing for hereditary syndrome (PMID: 31159747). The mutation database ClinVar contains entries for this variant (Variation ID: 220719). .
Baylor Genetics RCV000411352 SCV001525046 pathogenic Nijmegen breakage syndrome-like disorder 2019-01-07 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
CZECANCA consortium RCV001270999 SCV001451811 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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