rs201076557
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_080680.3(COL11A2):c.2254G>A(p.Val752Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,612,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_080680.3 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 |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.2254G>A | p.Val752Met | missense_variant | 29/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.2254G>A | p.Val752Met | missense_variant | 29/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.1996G>A | p.Val666Met | missense_variant | 27/64 | 5 | A1 | ||
COL11A2 | ENST00000361917.6 | c.829G>A | p.Val277Met | missense_variant | 16/24 | 5 | |||
COL11A2 | ENST00000477772.1 | n.272+979G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000142 AC: 35AN: 247050Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134560
GnomAD4 exome AF: 0.000341 AC: 498AN: 1460794Hom.: 1 Cov.: 35 AF XY: 0.000341 AC XY: 248AN XY: 726712
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152092Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74270
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | COL11A2: PM2 - |
Otospondylomegaepiphyseal dysplasia, autosomal dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 25, 2022 | Variant summary: COL11A2 c.2254G>A (p.Val752Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 247050 control chromosomes (gnomAD), predominantly at a frequency of 0.00028 within the Non-Finnish European subpopulation in the gnomAD database. c.2254G>A has been reported in the literature in at least one individual affected with hearing loss (Sommen_2016). The variant was also found in the homozygous state in an individual with facial dysmorphology, intellectual disability/developmental delay, muscle weakness and pain, and poor growth; this individual also carried a de novo pathogenic variant in QRICH1 (c.1953dup, p.Arg652fs) which was concordant with their observed phenotype (Ververi_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance, two as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. - |
Fibrochondrogenesis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Otospondylomegaepiphyseal dysplasia, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at