2-237361149-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM1BP6
The NM_004369.4(COL6A3):c.6182G>A(p.Arg2061Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,990 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_004369.4 missense
Scores
Clinical Significance
Conservation
Publications
- Bethlem myopathy 1AInheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics
- collagen 6-related myopathyInheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
- Ullrich congenital muscular dystrophy 1CInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- dystonia 27Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
- Ullrich congenital muscular dystrophy 1AInheritance: AR, AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
- Bethlem myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ullrich congenital muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.6182G>A | p.Arg2061Gln | missense_variant | Exon 16 of 44 | ENST00000295550.9 | NP_004360.2 | |
COL6A3 | NM_057167.4 | c.5564G>A | p.Arg1855Gln | missense_variant | Exon 15 of 43 | NP_476508.2 | ||
COL6A3 | NM_057166.5 | c.4361G>A | p.Arg1454Gln | missense_variant | Exon 13 of 41 | NP_476507.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.6182G>A | p.Arg2061Gln | missense_variant | Exon 16 of 44 | 1 | NM_004369.4 | ENSP00000295550.4 | ||
COL6A3 | ENST00000472056.5 | c.4361G>A | p.Arg1454Gln | missense_variant | Exon 13 of 41 | 1 | ENSP00000418285.1 | |||
COL6A3 | ENST00000353578.9 | c.5564G>A | p.Arg1855Gln | missense_variant | Exon 15 of 43 | 5 | ENSP00000315873.4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251450 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727218 show subpopulations
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340 show subpopulations
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.6182G>A (p.R2061Q) alteration is located in exon 16 (coding exon 15) of the COL6A3 gene. This alteration results from a G to A substitution at nucleotide position 6182, causing the arginine (R) at amino acid position 2061 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Bethlem myopathy 1A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at