rs372751467
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_020812.4(DOCK6):c.3562C>T(p.Gln1188*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,982 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 Likely 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.3562C>T | p.Gln1188* | stop_gained | 29/48 | ENST00000294618.12 | NP_065863.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOCK6 | ENST00000294618.12 | c.3562C>T | p.Gln1188* | stop_gained | 29/48 | 1 | NM_020812.4 | ENSP00000294618.6 | ||
DOCK6 | ENST00000587656.6 | c.3667C>T | p.Gln1223* | stop_gained | 30/49 | 5 | ENSP00000468638.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000284 AC: 7AN: 246826Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134270
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460780Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 726596
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2023 | This sequence change creates a premature translational stop signal (p.Gln1188*) 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 (rs372751467, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DOCK6-related conditions. ClinVar contains an entry for this variant (Variation ID: 499360). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 21, 2016 | - - |
Adams-Oliver syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Aug 14, 2018 | - - |
DOCK6-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2023 | The DOCK6 c.3562C>T variant is predicted to result in premature protein termination (p.Gln1188*). To our knowledge, this variant has not been reported in a patient with a DOCK6 related disorder. This variant is reported in 0.0057% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-11328056-G-A). Nonsense variants in DOCK6 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at