rs568049240
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_020812.4(DOCK6):c.4480G>T(p.Glu1494Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,000 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020812.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DOCK6 | NM_020812.4 | c.4480G>T | p.Glu1494Ter | stop_gained | 35/48 | ENST00000294618.12 | NP_065863.2 | |
LOC105372273 | NR_134909.1 | n.538-2950C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOCK6 | ENST00000294618.12 | c.4480G>T | p.Glu1494Ter | stop_gained | 35/48 | 1 | NM_020812.4 | ENSP00000294618 | A2 | |
ENST00000588634.1 | n.538-2950C>A | intron_variant, non_coding_transcript_variant | 4 | |||||||
DOCK6 | ENST00000587656.6 | c.4585G>T | p.Glu1529Ter | stop_gained | 36/49 | 5 | ENSP00000468638 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000727 AC: 18AN: 247732Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134678
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1459798Hom.: 0 Cov.: 31 AF XY: 0.0000276 AC XY: 20AN XY: 725914
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74344
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | This sequence change creates a premature translational stop signal (p.Glu1494*) in the DOCK6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DOCK6 are known to be pathogenic (PMID: 21820096, 25824905). This variant is present in population databases (rs568049240, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Adams-Olive syndrome (PMID: 25091416, 28884918). ClinVar contains an entry for this variant (Variation ID: 522048). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at