rs121912735
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_170665.4(ATP2A2):c.2682C>A(p.Tyr894Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ATP2A2
NM_170665.4 stop_gained
NM_170665.4 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 0.191
Genes affected
ATP2A2 (HGNC:812): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-110345323-C-A is Pathogenic according to our data. Variant chr12-110345323-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 17797.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-110345323-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A2 | NM_170665.4 | c.2682C>A | p.Tyr894Ter | stop_gained | 18/20 | ENST00000539276.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A2 | ENST00000539276.7 | c.2682C>A | p.Tyr894Ter | stop_gained | 18/20 | 1 | NM_170665.4 | P3 | |
ATP2A2 | ENST00000308664.10 | c.2682C>A | p.Tyr894Ter | stop_gained | 18/21 | 1 | A1 | ||
ATP2A2 | ENST00000548169.2 | c.2355C>A | p.Tyr785Ter | stop_gained | 14/16 | 2 | |||
ATP2A2 | ENST00000377685.9 | c.*2522C>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/20 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Darier disease, segmental Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at