ClinVar Miner

Submissions for variant NM_005431.2(XRCC2):c.440T>A (p.Ile147Asn)

gnomAD frequency: 0.00002  dbSNP: rs776710231
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022442 SCV001184178 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-30 criteria provided, single submitter clinical testing The p.I147N variant (also known as c.440T>A), located in coding exon 3 of the XRCC2 gene, results from a T to A substitution at nucleotide position 440. The isoleucine at codon 147 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001361438 SCV001557414 uncertain significance not provided 2024-03-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 147 of the XRCC2 protein (p.Ile147Asn). This variant is present in population databases (rs776710231, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with XRCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 824871). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt XRCC2 protein function with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV005036295 SCV005667304 uncertain significance Fanconi anemia complementation group U; Spermatogenic failures 50; Premature ovarian failure 17 2024-04-11 criteria provided, single submitter clinical testing

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