1-62508023-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001367561.1(DOCK7):c.4415A>G(p.Asp1472Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001367561.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DOCK7 | NM_001367561.1 | c.4415A>G | p.Asp1472Gly | missense_variant | Exon 35 of 50 | ENST00000635253.2 | NP_001354490.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250442Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135348
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1460794Hom.: 0 Cov.: 30 AF XY: 0.0000564 AC XY: 41AN XY: 726654
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74384
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 23 Uncertain:3
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This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1463 of the DOCK7 protein (p.Asp1463Gly). This variant is present in population databases (rs770382237, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DOCK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 475148). 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 DOCK7 protein function. 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. -
Inborn genetic diseases Uncertain:1
The c.4322A>G (p.D1441G) alteration is located in exon 34 (coding exon 34) of the DOCK7 gene. This alteration results from a A to G substitution at nucleotide position 4322, causing the aspartic acid (D) at amino acid position 1441 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at