13-25828127-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016529.6(ATP8A2):​c.2689G>T​(p.Ala897Ser) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ATP8A2
NM_016529.6 missense

Scores

1
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60
Variant links:
Genes affected
ATP8A2 (HGNC:13533): (ATPase phospholipid transporting 8A2) The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.419334).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATP8A2NM_016529.6 linkuse as main transcriptc.2689G>T p.Ala897Ser missense_variant 28/37 ENST00000381655.7 NP_057613.4 Q9NTI2-4Q6ZU25

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP8A2ENST00000381655.7 linkuse as main transcriptc.2689G>T p.Ala897Ser missense_variant 28/371 NM_016529.6 ENSP00000371070.2 Q9NTI2-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.00051
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.043
.;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Benign
-0.71
T
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.5
D;.
REVEL
Uncertain
0.35
Sift
Benign
0.33
T;.
Sift4G
Benign
0.26
T;T
Vest4
0.64
MVP
0.70
MPC
0.84
ClinPred
0.97
D
GERP RS
4.4
Varity_R
0.34
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1171835963; hg19: chr13-26402265; API