NM_001849.4:c.1358G>A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001849.4(COL6A2):c.1358G>A(p.Arg453His) variant causes a missense change. The variant allele was found at a frequency of 0.000075 in 1,479,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1358G>A | p.Arg453His | missense_variant | Exon 16 of 28 | ENST00000300527.9 | NP_001840.3 | |
COL6A2 | NM_058174.3 | c.1358G>A | p.Arg453His | missense_variant | Exon 16 of 28 | NP_478054.2 | ||
COL6A2 | NM_058175.3 | c.1358G>A | p.Arg453His | missense_variant | Exon 16 of 28 | NP_478055.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1358G>A | p.Arg453His | missense_variant | Exon 16 of 28 | 1 | NM_001849.4 | ENSP00000300527.4 | ||
COL6A2 | ENST00000397763.6 | c.1358G>A | p.Arg453His | missense_variant | Exon 16 of 28 | 5 | ENSP00000380870.1 | |||
COL6A2 | ENST00000409416.6 | c.1358G>A | p.Arg453His | missense_variant | Exon 15 of 27 | 5 | ENSP00000387115.1 | |||
COL6A2 | ENST00000413758.1 | c.-20G>A | upstream_gene_variant | 3 | ENSP00000395751.1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152130Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000803 AC: 7AN: 87126Hom.: 0 AF XY: 0.000133 AC XY: 6AN XY: 45154
GnomAD4 exome AF: 0.0000746 AC: 99AN: 1327312Hom.: 0 Cov.: 32 AF XY: 0.0000769 AC XY: 50AN XY: 650282
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152130Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:4
The R453H variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was notobserved in approximately 5,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The R453H variant is aconservative amino acid substitution, which is not likely to impact secondary protein structure as theseresidues share similar properties. However, this substitution occurs at a position that is conserved acrossspecies, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging tothe protein structure/function. -
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COL6A2: PP3 -
not specified Uncertain:1
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Bethlem myopathy 1A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at