rs267606747
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001849.4(COL6A2):āc.2329T>Cā(p.Cys777Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ). Synonymous variant affecting the same amino acid position (i.e. C777C) has been classified as Likely benign.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2329T>C | p.Cys777Arg | missense_variant | 26/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.2329T>C | p.Cys777Arg | missense_variant | 26/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.2329T>C | p.Cys777Arg | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2329T>C | p.Cys777Arg | missense_variant | 26/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.2329T>C | p.Cys777Arg | missense_variant | 26/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.2329T>C | p.Cys777Arg | missense_variant | 25/27 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248430Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134756
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458810Hom.: 0 Cov.: 37 AF XY: 0.00000551 AC XY: 4AN XY: 725804
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This variant is present in population databases (rs267606747, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt COL6A2 protein function. ClinVar contains an entry for this variant (Variation ID: 17166). This missense change has been observed in individuals with autosomal recessive Ullrich congenital muscular dystrophy (PMID: 15689448, 19564581, 22075033, 23940025). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 777 of the COL6A2 protein (p.Cys777Arg). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Jan 01, 2019 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 20, 2021 | - - |
Ullrich congenital muscular dystrophy 1B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 07, 2009 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at