6-33173749-TG-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_080680.3(COL11A2):c.2584-5delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,594,094 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 4 hom. )
Consequence
COL11A2
NM_080680.3 splice_region, intron
NM_080680.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.994
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 -16 ACMG points.
BP6
Variant 6-33173749-TG-T is Benign according to our data. Variant chr6-33173749-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 227266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33173749-TG-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00106 (160/151480) while in subpopulation NFE AF= 0.00196 (133/67788). AF 95% confidence interval is 0.00169. There are 1 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
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COL11A2 | NM_080680.3 | c.2584-5delC | splice_region_variant, intron_variant | ENST00000341947.7 | NP_542411.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL11A2 | ENST00000341947.7 | c.2584-5delC | splice_region_variant, intron_variant | 5 | NM_080680.3 | ENSP00000339915.2 | ||||
COL11A2 | ENST00000374708.8 | c.2326-5delC | splice_region_variant, intron_variant | 5 | ENSP00000363840.4 | |||||
COL11A2 | ENST00000361917.6 | c.1156-5delC | splice_region_variant, intron_variant | 5 | ENSP00000355123.2 | |||||
COL11A2 | ENST00000477772.1 | n.272+3259delC | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 160AN: 151362Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00124 AC: 298AN: 239644Hom.: 2 AF XY: 0.00134 AC XY: 174AN XY: 129382
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GnomAD4 exome AF: 0.00148 AC: 2141AN: 1442614Hom.: 4 Cov.: 36 AF XY: 0.00143 AC XY: 1023AN XY: 714712
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GnomAD4 genome AF: 0.00106 AC: 160AN: 151480Hom.: 1 Cov.: 32 AF XY: 0.00103 AC XY: 76AN XY: 74034
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | COL11A2: BP4, BS2 - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 26, 2017 | c.2584-5delC in intron 34 of COL11A2: This variant is not expected to have clin ical significance because this variant has been identified in 0.21% (254/121798) of European chromosomes including 2 homozygotes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs555657704). Furthermore, computational tools do not predict an impact to splicing. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 28, 2016 | - - |
Otospondylomegaepiphyseal dysplasia, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Otospondylomegaepiphyseal dysplasia, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Fibrochondrogenesis 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Stickler Syndrome, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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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