chr12-47978673-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PM1PP2BP4BS1BS2
The NM_001844.5(COL2A1):c.2819G>A(p.Arg940Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,326 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R940P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001844.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL2A1 | NM_001844.5 | c.2819G>A | p.Arg940Gln | missense_variant | 42/54 | ENST00000380518.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.2819G>A | p.Arg940Gln | missense_variant | 42/54 | 1 | NM_001844.5 | P1 | |
COL2A1 | ENST00000337299.7 | c.2612G>A | p.Arg871Gln | missense_variant | 41/53 | 1 | |||
COL2A1 | ENST00000493991.5 | n.1905G>A | non_coding_transcript_exon_variant | 25/37 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000375 AC: 57AN: 152100Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000248 AC: 62AN: 249568Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135374
GnomAD4 exome AF: 0.0000753 AC: 110AN: 1461108Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 49AN XY: 726850
GnomAD4 genome AF: 0.000374 AC: 57AN: 152218Hom.: 1 Cov.: 32 AF XY: 0.000605 AC XY: 45AN XY: 74426
ClinVar
Submissions by phenotype
Stickler syndrome type 1 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Stickler syndrome, type I, nonsyndromic ocular Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Miami Human Genetics, University Of Miami Miller School Of Medicine | May 09, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Type II Collagenopathies 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at