rs201785518
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The ENST00000357997.10(ANKLE2):c.2344C>T(p.Gln782Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000357997.10 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ANKLE2 | NM_015114.3 | c.2344C>T | p.Gln782Ter | stop_gained | 11/13 | ENST00000357997.10 | NP_055929.1 | |
ANKLE2 | XM_005266159.4 | c.2158C>T | p.Gln720Ter | stop_gained | 11/13 | XP_005266216.1 | ||
ANKLE2 | XM_024448899.2 | c.1033C>T | p.Gln345Ter | stop_gained | 7/9 | XP_024304667.1 | ||
ANKLE2 | XM_006719735.2 | c.1892-1655C>T | intron_variant | XP_006719798.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ANKLE2 | ENST00000357997.10 | c.2344C>T | p.Gln782Ter | stop_gained | 11/13 | 1 | NM_015114.3 | ENSP00000350686 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151562Hom.: 0 Cov.: 26
GnomAD3 exomes AF: 0.0000563 AC: 14AN: 248756Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135232
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461564Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727080
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151680Hom.: 0 Cov.: 26 AF XY: 0.0000270 AC XY: 2AN XY: 74120
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; This variant is associated with the following publications: (PMID: 31735666, 30086807, 25259927) - |
Microcephaly 16, primary, autosomal recessive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 25, 2014 | - - |
Microcephaly Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Sep 25, 2014 | Overexpression of human cDNA carring this variant does not rescue mutant fly - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at