rs200587951
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_022089.4(ATP13A2):c.106-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00095 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_022089.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP13A2 | NM_022089.4 | c.106-8G>A | splice_region_variant, intron_variant | Intron 2 of 28 | ENST00000326735.13 | NP_071372.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP13A2 | ENST00000326735.13 | c.106-8G>A | splice_region_variant, intron_variant | Intron 2 of 28 | 1 | NM_022089.4 | ENSP00000327214.8 | |||
ENSG00000288636 | ENST00000617114.5 | c.125-8G>A | splice_region_variant, intron_variant | Intron 2 of 3 | 5 | ENSP00000478781.2 |
Frequencies
GnomAD3 genomes AF: 0.000716 AC: 109AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000925 AC: 232AN: 250896Hom.: 0 AF XY: 0.000950 AC XY: 129AN XY: 135788
GnomAD4 exome AF: 0.000974 AC: 1424AN: 1461864Hom.: 1 Cov.: 33 AF XY: 0.000991 AC XY: 721AN XY: 727230
GnomAD4 genome AF: 0.000716 AC: 109AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.000686 AC XY: 51AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -
ATP13A2: BP4 -
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Kufor-Rakeb syndrome Uncertain:1Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
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not specified Uncertain:1
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Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at