rs34479977
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020812.4(DOCK6):āc.4216T>Gā(p.Ser1406Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,764 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. S1406S) has been classified as Likely benign.
Frequency
Consequence
NM_020812.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK6 | NM_020812.4 | c.4216T>G | p.Ser1406Ala | missense_variant | 34/48 | ENST00000294618.12 | |
LOC105372273 | NR_134909.1 | n.538-1740A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK6 | ENST00000294618.12 | c.4216T>G | p.Ser1406Ala | missense_variant | 34/48 | 1 | NM_020812.4 | A2 | |
ENST00000588634.1 | n.538-1740A>C | intron_variant, non_coding_transcript_variant | 4 | ||||||
DOCK6 | ENST00000587656.6 | c.4321T>G | p.Ser1441Ala | missense_variant | 35/49 | 5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000185 AC: 46AN: 249140Hom.: 0 AF XY: 0.000178 AC XY: 24AN XY: 135190
GnomAD4 exome AF: 0.000140 AC: 204AN: 1461498Hom.: 1 Cov.: 34 AF XY: 0.000144 AC XY: 105AN XY: 727008
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 25, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1406 of the DOCK6 protein (p.Ser1406Ala). This variant is present in population databases (rs34479977, gnomAD 0.08%). 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: 235741). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DOCK6 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Adams-Oliver syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 27, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
DOCK6-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2024 | The DOCK6 c.4216T>G variant is predicted to result in the amino acid substitution p.Ser1406Ala. To our knowledge, this variant has not been reported in the literature in individuals with DOCK6-related disorders. This variant is reported in 0.073% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at