rs149248784
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_007357.3(COG2):c.2026G>A(p.Ala676Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,613,960 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_007357.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COG2 | NM_007357.3 | c.2026G>A | p.Ala676Thr | missense_variant | 17/18 | ENST00000366669.9 | NP_031383.1 | |
COG2 | NM_001145036.2 | c.2023G>A | p.Ala675Thr | missense_variant | 17/18 | NP_001138508.1 | ||
COG2 | XM_047449445.1 | c.1687G>A | p.Ala563Thr | missense_variant | 15/16 | XP_047305401.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG2 | ENST00000366669.9 | c.2026G>A | p.Ala676Thr | missense_variant | 17/18 | 1 | NM_007357.3 | ENSP00000355629.4 |
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000450 AC: 113AN: 251358Hom.: 0 AF XY: 0.000589 AC XY: 80AN XY: 135868
GnomAD4 exome AF: 0.000471 AC: 688AN: 1461844Hom.: 1 Cov.: 30 AF XY: 0.000481 AC XY: 350AN XY: 727216
GnomAD4 genome AF: 0.000296 AC: 45AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74298
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation, type IIq Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 13, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 676 of the COG2 protein (p.Ala676Thr). This variant is present in population databases (rs149248784, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with COG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 579951). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at