ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.190C>T (p.Arg64Ter)

gnomAD frequency: 0.00003  dbSNP: rs151110146
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572575 SCV000675849 pathogenic Hereditary cancer-predisposing syndrome 2022-03-31 criteria provided, single submitter clinical testing The p.R64* variant (also known as c.190C>T), located in coding exon 3 of the XRCC2 gene, results from a C to T substitution at nucleotide position 190. This changes the amino acid from an arginine to a stop codon within coding exon 3. This alteration was seen in one patient from a Chinese breast cancer cohort (Sun J et al. Clin. Cancer Res. 2017 Oct;23(20):6113-6119). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
GeneKor MSA RCV000572575 SCV000821789 likely pathogenic Hereditary cancer-predisposing syndrome 2020-01-01 criteria provided, single submitter clinical testing This variant is a single amino acid change from Arginine to a premature translational stop signal at codon 64 of the XRCC2 protein. This is expected to result in an absent or disrupted protein product. This variant has been described in the international literature in individuals undergoing panel testing for hereditary syndrome (PMID: 31159747).
Labcorp Genetics (formerly Invitae), Labcorp RCV001312491 SCV001502947 uncertain significance not provided 2024-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg64*) in the XRCC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 217 amino acid(s) of the XRCC2 protein. This variant is present in population databases (rs151110146, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with a personal or family history of breast and/or ovarian cancer and/or pancreatic ductal adenocarcinoma (PMID: 28724667, 31159747, 35171259). ClinVar contains an entry for this variant (Variation ID: 486729). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV000572575 SCV002538365 likely pathogenic Hereditary cancer-predisposing syndrome 2021-05-29 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV005034145 SCV005667308 likely pathogenic Fanconi anemia complementation group U; Spermatogenic failures 50; Premature ovarian failure 17 2024-03-16 criteria provided, single submitter clinical testing

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