rs147576338
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_080680.3(COL11A2):c.3616C>T(p.Leu1206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,082 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 3 hom. )
Consequence
COL11A2
NM_080680.3 synonymous
NM_080680.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
COL11A2 (HGNC:2187): (collagen type XI alpha 2 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 6-33170067-G-A is Benign according to our data. Variant chr6-33170067-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178325.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Uncertain_significance=3, Benign=1}. Variant chr6-33170067-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000151 (23/152292) while in subpopulation SAS AF= 0.00207 (10/4828). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL11A2 | NM_080680.3 | c.3616C>T | p.Leu1206= | synonymous_variant | 49/66 | ENST00000341947.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.3616C>T | p.Leu1206= | synonymous_variant | 49/66 | 5 | NM_080680.3 | P4 | |
COL11A2 | ENST00000374708.8 | c.3358C>T | p.Leu1120= | synonymous_variant | 47/64 | 5 | A1 | ||
COL11A2 | ENST00000477772.1 | n.273-4251C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000344 AC: 85AN: 247150Hom.: 0 AF XY: 0.000409 AC XY: 55AN XY: 134548
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GnomAD4 exome AF: 0.000211 AC: 308AN: 1460790Hom.: 3 Cov.: 34 AF XY: 0.000267 AC XY: 194AN XY: 726706
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74456
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | COL11A2: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 24, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Otospondylomegaepiphyseal dysplasia, autosomal recessive 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. - |
Fibrochondrogenesis 2 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. - |
Otospondylomegaepiphyseal dysplasia, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 28, 2015 | p.Leu1206Leu in exon 49 of COL11A2: This variant is not expected to have clinica l significance because it does not alter an amino acid residue and is not locate d within the splice consensus sequence. It has been identified in 0.2% (38/16314 ) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs147576338). - |
COL11A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 25, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Stickler Syndrome, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at