rs754744977
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014908.4(DOLK):c.194A>G(p.Gln65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014908.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOLK | NM_014908.4 | c.194A>G | p.Gln65Arg | missense_variant | 1/1 | ENST00000372586.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOLK | ENST00000372586.4 | c.194A>G | p.Gln65Arg | missense_variant | 1/1 | NM_014908.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250620Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135618
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461738Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727186
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152136Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74320
ClinVar
Submissions by phenotype
DK1-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | This variant is present in population databases (rs754744977, gnomAD 0.0009%). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 532848). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 65 of the DOLK protein (p.Gln65Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at