rs796052282
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_000702.4(ATP1A2):c.192G>T(p.Gln64His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000702.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.192G>T | p.Gln64His | missense_variant | 4/23 | ENST00000361216.8 | NP_000693.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.192G>T | p.Gln64His | missense_variant | 4/23 | 1 | NM_000702.4 | ENSP00000354490.3 | ||
ATP1A2 | ENST00000392233.7 | c.192G>T | p.Gln64His | missense_variant | 4/23 | 5 | ENSP00000376066.3 | |||
ATP1A2 | ENST00000472488.5 | n.295G>T | non_coding_transcript_exon_variant | 4/20 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727240
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 02, 2022 | The c.192G>T (p.Q64H) alteration is located in exon 4 (coding exon 4) of the ATP1A2 gene. This alteration results from a G to T substitution at nucleotide position 192, causing the glutamine (Q) at amino acid position 64 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 14, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
ATP1A2-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 06, 2024 | The ATP1A2 c.192G>T variant is predicted to result in the amino acid substitution p.Gln64His. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Familial hemiplegic migraine Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 64 of the ATP1A2 protein (p.Gln64His). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. 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. 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 ATP1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 204910). - |
Migraine, familial hemiplegic, 2;C3549447:Alternating hemiplegia of childhood 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at