ClinVar Miner

Submissions for variant NM_000052.7(ATP7A):c.2957G>A (p.Arg986Gln)

gnomAD frequency: 0.00001  dbSNP: rs781995242
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235979 SCV000293056 uncertain significance not provided 2018-04-18 criteria provided, single submitter clinical testing The R986Q variant in the ATP7A gene has been reported previously in a patient with Menkes disease, in a publication following body weight and height in individuals treated with copper-histidine after 1 month of birth. No additional variant specific nor patient specific information was included in the publication (Gu et al., 2014). The R986Q variant is observed in 1/12870 (0.008%) alleles from individuals of East Asian background, in large population cohorts (Lek et al., 2016). The R986Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret R986Q as a variant of uncertain significance,
Labcorp Genetics (formerly Invitae), Labcorp RCV002518435 SCV003249741 uncertain significance Menkes kinky-hair syndrome; Cutis laxa, X-linked; X-linked distal spinal muscular atrophy type 3 2022-09-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 986 of the ATP7A protein (p.Arg986Gln). This variant is present in population databases (rs781995242, gnomAD 0.008%). This missense change has been observed in individual(s) with Menkes disease (PMID: 30809870). This variant is also known as c.3102G>A. ClinVar contains an entry for this variant (Variation ID: 245881). 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 not expected to disrupt ATP7A 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.

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