Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000996033 | SCV001150471 | uncertain significance | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV003448355 | SCV004176143 | uncertain significance | X-linked progressive cerebellar ataxia | 2023-09-01 | criteria provided, single submitter | clinical testing | The c.2105G>A variant in ATP2B3 has not previously been reported in the literature; it has been deposited in ClinVar [ClinVar ID: 807831] as Variant of Uncertain Significance with affected status provided. The c.2105G>A is observed in 22 alleles (~0.0044% minor allele frequency with 3 hemizygotes and 2 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.2105G>A variant is located in exon 14 of this 22-exon gene and predicted to replace an evolutionarily conserved arginine amino acid with histidine at position 702 within the p-type ATPase domain of the encoded protein [UniProt ID: Q16720]. In silico predictions are in favor of damaging effect for the p.(Arg702His) variant [(CADD v1.6 = 28.9, REVEL = 0.944)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this maternally inherited hemizygous c.2105G>A p.(Arg702His) variant identified in ATP2B3 is classified as a Variant of Uncertain Significance. |