rs200587951
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000326735.13(ATP13A2):c.106-8G>A variant causes a splice region, splice polypyrimidine tract, 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
ENST00000326735.13 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP13A2 | NM_022089.4 | c.106-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000326735.13 | NP_071372.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP13A2 | ENST00000326735.13 | c.106-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_022089.4 | ENSP00000327214 | A1 | |||
ENST00000617114.5 | c.125-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | ENSP00000478781 | P1 |
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
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | ATP13A2: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 08, 2024 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 16, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Kufor-Rakeb syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 28, 2014 | - - |
Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at