chr12-110342435-G-A
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PS1PM1PM2PP2PP3_StrongPP5_Moderate
The ENST00000539276.7(ATP2A2):c.2305G>A(p.Gly769Arg) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd.
Frequency
Consequence
ENST00000539276.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP2A2 | NM_170665.4 | c.2305G>A | p.Gly769Arg | missense_variant | 15/20 | ENST00000539276.7 | NP_733765.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP2A2 | ENST00000539276.7 | c.2305G>A | p.Gly769Arg | missense_variant | 15/20 | 1 | NM_170665.4 | ENSP00000440045 | P3 | |
ATP2A2 | ENST00000308664.10 | c.2305G>A | p.Gly769Arg | missense_variant | 15/21 | 1 | ENSP00000311186 | A1 | ||
ATP2A2 | ENST00000548169.2 | c.1978G>A | p.Gly660Arg | missense_variant | 11/16 | 2 | ENSP00000449454 | |||
ATP2A2 | ENST00000377685.9 | c.*2145G>A | 3_prime_UTR_variant, NMD_transcript_variant | 14/20 | 5 | ENSP00000366913 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Darier disease, segmental Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2000 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2019 | Published functional studies demonstrate protein expression level was higher than 30% of wild type, but the variant completely abolished Ca2+-ATPase activity and Ca2+ transport activity, resulting in severe disruption of Ca2+ homeostasis (Miyauchi et al., 2006); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28035777, 11121153, 16766529, 22035154) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at