13-25372280-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016529.6(ATP8A2):c.68C>G(p.Ser23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,431,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S23S) has been classified as Likely benign.
Frequency
Consequence
NM_016529.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP8A2 | NM_016529.6 | c.68C>G | p.Ser23Trp | missense_variant | 1/37 | ENST00000381655.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP8A2 | ENST00000381655.7 | c.68C>G | p.Ser23Trp | missense_variant | 1/37 | 1 | NM_016529.6 |
Frequencies
GnomAD3 genomes ? AF: 0.000264 AC: 40AN: 151340Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000212 AC: 20AN: 94198Hom.: 0 AF XY: 0.000228 AC XY: 12AN XY: 52630
GnomAD4 exome AF: 0.000503 AC: 644AN: 1280390Hom.: 0 Cov.: 31 AF XY: 0.000508 AC XY: 321AN XY: 631776
GnomAD4 genome ? AF: 0.000264 AC: 40AN: 151446Hom.: 0 Cov.: 32 AF XY: 0.000216 AC XY: 16AN XY: 74054
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The c.68C>G (p.S23W) alteration is located in exon 1 (coding exon 1) of the ATP8A2 gene. This alteration results from a C to G substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a tryptophan (W). 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 | Invitae | Jun 10, 2022 | This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 23 of the ATP8A2 protein (p.Ser23Trp). This variant is present in population databases (rs200068509, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ATP8A2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at