rs2855437

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080680.3(COL11A2):c.3313-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,610,246 control chromosomes in the GnomAD database, including 409,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41958 hom., cov: 31)

Exomes 𝑓: 0.71 ( 367758 hom. )

Consequence

COL11A2
NM_080680.3 intron

Scores

Splicing: ADA: 0.00001617

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 0.398

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=-0.82).

BP6

Variant 6-33171178-G-A is Benign according to our data. Variant chr6-33171178-G-A is described in ClinVar as [Benign]. Clinvar id is 46566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33171178-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3 link	c.3313-11C>T		intron_variant	Intron 44 of 65	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 link	c.3313-11C>T	intron_variant	Intron 44 of 65	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 link	c.3055-11C>T	intron_variant	Intron 42 of 63	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000477772.1 link	n.273-5362C>T	intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112418

AN:

151924

Hom.:

41911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.759

Gnomad EAS

AF:

0.900

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.783

Gnomad NFE

AF:

0.691

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.744

AC:

181785

AN:

244222

Hom.:

68188

AF XY:

0.746

AC XY:

98435

AN XY:

132026

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.765

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.907

Gnomad SAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.694

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.708

AC:

1031882

AN:

1458204

Hom.:

367758

Cov.:

AF XY:

0.711

AC XY:

515820

AN XY:

725120

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.765

Gnomad4 ASJ exome

AF:

0.767

Gnomad4 EAS exome

AF:

0.945

Gnomad4 SAS exome

AF:

0.825

Gnomad4 FIN exome

AF:

0.695

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.740

AC:

112521

AN:

152042

Hom.:

41958

Cov.:

AF XY:

0.741

AC XY:

55112

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.801

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.759

Gnomad4 EAS

AF:

0.900

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.701

Gnomad4 NFE

AF:

0.691

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.712

Hom.:

65177

Bravo

AF:

0.745

Asia WGS

AF:

0.818

AC:

2844

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

3313-11C>T in Intron 44 of COL11A2: This variant is not expected to have clinica l significance because it has been identified in 31.5% (2213/7016) of European A merican chromosomes from a broad population by the NHLBI Exome Sequencing Projec t (http://evs.gs.washington.edu/EVS; dbSNP rs2855437). -

Mar 21, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Otospondylomegaepiphyseal dysplasia, autosomal dominant

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Otospondylomegaepiphyseal dysplasia, autosomal recessive

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibrochondrogenesis 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 53

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 13

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stickler Syndrome, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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