ClinVar Miner

Submissions for variant NM_001375.3(DNASE2):c.1079T>G (p.Ile360Ser)

gnomAD frequency: 0.00004  dbSNP: rs554384572
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001372953 SCV001569649 uncertain significance not provided 2021-10-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with serine at codon 360 of the DNASE2 protein (p.Ile360Ser). The isoleucine residue is weakly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is present in population databases (rs554384572, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with DNASE2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
PreventionGenetics, part of Exact Sciences RCV003416293 SCV004117023 uncertain significance DNASE2-related disorder 2022-10-27 criteria provided, single submitter clinical testing The DNASE2 c.1079T>G variant is predicted to result in the amino acid substitution p.Ile360Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-12986808-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004037548 SCV004860176 likely benign not specified 2023-12-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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