ClinVar Miner

Submissions for variant NM_152383.5(DIS3L2):c.1876G>A (p.Asp626Asn)

gnomAD frequency: 0.00005  dbSNP: rs374482102
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000476550 SCV000551591 uncertain significance Perlman syndrome 2024-09-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 626 of the DIS3L2 protein (p.Asp626Asn). This variant is present in population databases (rs374482102, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DIS3L2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410730). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DIS3L2 protein function with a negative 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 RCV000476550 SCV002779067 uncertain significance Perlman syndrome 2021-09-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004022813 SCV004857829 uncertain significance Inborn genetic diseases 2024-01-08 criteria provided, single submitter clinical testing The c.1876G>A (p.D626N) alteration is located in exon 15 (coding exon 14) of the DIS3L2 gene. This alteration results from a G to A substitution at nucleotide position 1876, causing the aspartic acid (D) at amino acid position 626 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000476550 SCV005688994 uncertain significance Perlman syndrome 2024-07-17 criteria provided, single submitter clinical testing The DIS3L2 c.1876G>A (p.Asp626Asn) missense change has a maximum subpopulation frequency of 0.004% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Perlman syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?

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