rs139399166
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001849.4(COL6A2):c.988G>A(p.Asp330Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000489 in 1,612,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D330V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.988G>A | p.Asp330Asn | missense_variant | 10/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.988G>A | p.Asp330Asn | missense_variant | 10/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.988G>A | p.Asp330Asn | missense_variant | 10/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.988G>A | p.Asp330Asn | missense_variant | 10/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.988G>A | p.Asp330Asn | missense_variant | 10/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.988G>A | p.Asp330Asn | missense_variant | 9/27 | 5 | |||
COL6A2 | ENST00000485591.1 | n.644G>A | non_coding_transcript_exon_variant | 6/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000332 AC: 83AN: 249986Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135634
GnomAD4 exome AF: 0.000507 AC: 741AN: 1460652Hom.: 0 Cov.: 36 AF XY: 0.000493 AC XY: 358AN XY: 726604
GnomAD4 genome AF: 0.000309 AC: 47AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2023 | Reported previously in an individual with macular degeneration with no reported history of muscle disease (Seddon et al., 2013); Reported as a germline variant in an individual with gastric cancer, although no evidence of pathogenicity or further clinical information were provided (Vogelaar et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24036952, 28875981, 30564623, 31805011) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 23, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 27, 2017 | - - |
Myosclerosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at