ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.378_381del (p.Leu126fs)

dbSNP: rs763401560
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000481611 SCV000949874 uncertain significance not provided 2022-08-09 criteria provided, single submitter clinical testing Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant 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. ClinVar contains an entry for this variant (Variation ID: 420463). This variant has not been reported in the literature in individuals affected with XRCC2-related conditions. This variant is present in population databases (rs763401560, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Leu126Phefs*7) in the XRCC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 155 amino acid(s) of the XRCC2 protein.
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 2022-07-12 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). This alteration occurs at the 3' terminus of XRCC2 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 149 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000988017 SCV002512469 likely pathogenic Fanconi anemia complementation group U 2021-09-26 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 strong, PM2 moderate

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.