ClinVar Miner

Submissions for variant NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile)

gnomAD frequency: 0.00011  dbSNP: rs142013283
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001704969 SCV000240384 likely benign not provided 2019-12-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000640918 SCV000762522 uncertain significance Syndromic X-linked intellectual disability Hedera type 2024-12-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 164 of the ATP6AP2 protein (p.Val164Ile). This variant is present in population databases (rs142013283, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATP6AP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 204912). 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 ATP6AP2 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767901 SCV000898540 uncertain significance Syndromic X-linked intellectual disability Hedera type; X-linked parkinsonism-spasticity syndrome 2018-10-25 criteria provided, single submitter clinical testing ATP6AP2 NM_005765.2 exon 5 p.Val164Ile (c.490G>A): This variant has not been reported in the literature but is present in 3/27186 Latino alleles, including 1 hemizygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs142013283). This variant is present in ClinVar (Variation ID:204912). This variant amino acid Isoleucine (Ile) is present in >30 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224203 SCV003920281 uncertain significance Syndromic X-linked intellectual disability Hedera type; X-linked parkinsonism-spasticity syndrome; Congenital disorder of glycosylation, type IIr 2021-03-30 criteria provided, single submitter clinical testing ATP6AP2 NM_005765 exon 5 p.Val164Ile (c.490G>A): This variant has not been reported in the literature but is present in 3/27186 Latino alleles, including 1 hemizygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs142013283). This variant is present in ClinVar (Variation ID:204912). This variant amino acid Isoleucine (Ile) is present in >30 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004020260 SCV004913538 likely benign Inborn genetic diseases 2024-01-16 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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