ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.374_377ACTT[1] (p.Leu126fs) (rs763401560)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV001021119 SCV000838292 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV000481611 SCV000949874 uncertain significance not provided 2018-11-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the XRCC2 gene (p.Leu126Phefs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 155 amino acids of the XRCC2 protein. This variant is present in population databases (rs763401560, ExAC 0.009%). This variant has not been reported in the literature in individuals with XRCC2-related disease. ClinVar contains an entry for this variant (Variation ID: 420463). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Mendelics RCV000988017 SCV001137564 uncertain significance Fanconi anemia, complementation group U 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001021119 SCV001182696 pathogenic Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing The c.378_381delACTT pathogenic mutation, located in coding exon 3 of the XRCC2 gene, results from a deletion of 4 nucleotides at nucleotide positions 378 to 381, causing a translational frameshift with a predicted alternate stop codon (p.L126Ffs*7). 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.

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