rs35881321
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001849.4(COL6A2):c.679G>C(p.Asp227His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D227E) has been classified as Likely benign.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.679G>C | p.Asp227His | missense_variant | 3/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.679G>C | p.Asp227His | missense_variant | 3/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.679G>C | p.Asp227His | missense_variant | 3/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.679G>C | p.Asp227His | missense_variant | 3/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.679G>C | p.Asp227His | missense_variant | 3/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.679G>C | p.Asp227His | missense_variant | 2/27 | 5 | |||
COL6A2 | ENST00000460886.1 | n.125G>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | 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 COL6A2 protein function. ClinVar contains an entry for this variant (Variation ID: 476491). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 227 of the COL6A2 protein (p.Asp227His). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at