rs186720023

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_080680.3(COL11A2):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,986 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

COL11A2
NM_080680.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.435

Variant links:

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]

COL11A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-33163674-G-A is Benign according to our data. Variant chr6-33163674-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00181 (275/152222) while in subpopulation NFE AF= 0.00243 (165/68002). AF 95% confidence interval is 0.00212. There are 0 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3 linkuse as main transcript	c.*4C>T		3_prime_UTR_variant	66/66	ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
COL11A2	ENST00000341947.7 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	66/66	5	NM_080680.3	P4
COL11A2	ENST00000374708.8 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	64/64	5		A1
COL11A2	ENST00000477772.1 linkuse as main transcript	n.1005C>T	non_coding_transcript_exon_variant	9/9	2
COL11A2	ENST00000683572.1 linkuse as main transcript	n.1021C>T	non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

275

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00194

AC:

478

AN:

245946

Hom.:

AF XY:

0.00184

AC XY:

247

AN XY:

134098

show subpopulations

Gnomad AFR exome

AF:

0.000397

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00212

AC:

3090

AN:

1460764

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1521

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00529

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152222

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00123

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 14, 2024	Variant summary: COL11A2 c.4C>T affects a non-conserved nucleotide located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0021 in 1612986 control chromosomes in the gnomAD database, including 7 homozygotes (gnomAD v4.0.0). The available data on variant occurrences in the general population are insufficient to allow definitive conclusions about variant significance, but do suggest the variant likely represents a benign polymorphism. To our knowledge, no occurrence of c.4C>T in individuals affected with COL11A2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 178320). Based on the evidence outlined above, the variant was classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 31, 2016	4C>T in the 3'UTR of COL11A2: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (33/6604) of Finnish chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs186720023). In addition, a number of mammals have a T at the 4 position, including jerboa, mouse, black flying fox, megabat, and brown bat. -

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

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2022

See Variant Classification Assertion Criteria. -

Fibrochondrogenesis 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 01, 2020

- -

Stickler Syndrome, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

8.8

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over