rs121918612
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The ENST00000361216.8(ATP1A2):c.901G>A(p.Gly301Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G301E) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000361216.8 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP1A2 | NM_000702.4 | c.901G>A | p.Gly301Arg | missense_variant | 8/23 | ENST00000361216.8 | NP_000693.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP1A2 | ENST00000361216.8 | c.901G>A | p.Gly301Arg | missense_variant | 8/23 | 1 | NM_000702.4 | ENSP00000354490 | P1 | |
ATP1A2 | ENST00000392233.7 | c.901G>A | p.Gly301Arg | missense_variant | 8/23 | 5 | ENSP00000376066 | |||
ATP1A2 | ENST00000447527.1 | c.34G>A | p.Gly12Arg | missense_variant | 1/16 | 2 | ENSP00000411705 | |||
ATP1A2 | ENST00000472488.5 | n.1004G>A | non_coding_transcript_exon_variant | 8/20 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Familial hemiplegic migraine Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 19372756, 21398422). 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 expected to disrupt ATP1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 12922). This missense change has been observed in individuals with familial hemiplegic migraine (PMID: 15459825, 21398422). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 301 of the ATP1A2 protein (p.Gly301Arg). - |
not provided, no classification provided | literature only | GeneReviews | - | Severe phenotype reported - |
Migraine, familial hemiplegic, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2004 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at