rs141919484
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001849.4(COL6A2):āc.1913T>Gā(p.Val638Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V638I) has been classified as Likely benign.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1913T>G | p.Val638Gly | missense_variant | 25/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.1913T>G | p.Val638Gly | missense_variant | 25/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.1913T>G | p.Val638Gly | missense_variant | 25/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1913T>G | p.Val638Gly | missense_variant | 25/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.1913T>G | p.Val638Gly | missense_variant | 25/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.1913T>G | p.Val638Gly | missense_variant | 24/27 | 5 | |||
COL6A2 | ENST00000413758.1 | c.584T>G | p.Val195Gly | missense_variant | 10/11 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151832Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250508Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135816
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460622Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0AN XY: 726606
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151832Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74144
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2017 | This sequence change replaces valine with glycine at codon 638 of the COL6A2 protein (p.Val638Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COL6A2-related disease. This variant is present in population databases (rs141919484, ExAC 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at