rs140419176
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001849.4(COL6A2):c.2769C>A(p.His923Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H923R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001849.4 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 |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2769C>A | p.His923Gln | missense_variant | 28/28 | ENST00000300527.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2769C>A | p.His923Gln | missense_variant | 28/28 | 1 | NM_001849.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000169 AC: 4AN: 236200Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 129304
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453882Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2AN XY: 723358
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 03, 2018 | This sequence change replaces histidine with glutamine at codon 923 of the COL6A2 protein (p.His923Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL6A2-related disease. This variant is present in population databases (rs140419176, ExAC 0.03%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at