rs41266697

Positions:

chr6-33178344-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_080680.3(COL11A2):c.1782C>T(p.Asp594Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00756 in 1,612,264 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 52 hom. )

Consequence

COL11A2
NM_080680.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 0.0930

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-33178344-G-A is Benign according to our data. Variant chr6-33178344-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33178344-G-A is described in Lovd as [Benign]. Variant chr6-33178344-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.093 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00675 (1023/151514) while in subpopulation NFE AF= 0.00747 (507/67836). AF 95% confidence interval is 0.00694. There are 8 homozygotes in gnomad4. There are 460 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A2	NM_080680.3 linkuse as main transcript	c.1782C>T	p.Asp594Asp	synonymous_variant	20/66	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 linkuse as main transcript	c.1782C>T	p.Asp594Asp	synonymous_variant	20/66	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 linkuse as main transcript	c.1524C>T	p.Asp508Asp	synonymous_variant	18/64	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000361917.6 linkuse as main transcript	c.408C>T	p.Asp136Asp	synonymous_variant	8/24	5		ENSP00000355123.2	H0YIS1

Frequencies

GnomAD3 genomes

AF:

0.00676

AC:

1023

AN:

151398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00546

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00583

Gnomad FIN

AF:

0.00409

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00747

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00690

AC:

1702

AN:

246628

Hom.:

AF XY:

0.00689

AC XY:

926

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.00568

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.0213

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.00783

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00741

GnomAD4 exome

AF:

0.00765

AC:

11172

AN:

1460750

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

5553

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.00582

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00750

Gnomad4 FIN exome

AF:

0.00483

Gnomad4 NFE exome

AF:

0.00793

Gnomad4 OTH exome

AF:

0.00768

GnomAD4 genome

AF:

0.00675

AC:

1023

AN:

151514

Hom.:

Cov.:

AF XY:

0.00621

AC XY:

460

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.00545

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.00584

Gnomad4 FIN

AF:

0.00409

Gnomad4 NFE

AF:

0.00747

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00823

Hom.:

Bravo

AF:

0.00646

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00717

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 23, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2018	This variant is associated with the following publications: (PMID: no PMID) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	COL11A2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 15, 2022	- -
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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 09, 2017	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Asp594Asp in Exon 20 of COL11A2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.6% (29/4488) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs41266697). -

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

Fibrochondrogenesis 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 06, 2022

- -

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

-0.65

CADD

Benign

0.89

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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