rs143186319

Variant summary

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

The NM_080680.3(COL11A2):c.4458T>A(p.Gly1486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,613,790 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G1486G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

COL11A2
NM_080680.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.28

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=-0.84).

BP6

Variant 6-33165955-A-T is Benign according to our data. Variant chr6-33165955-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 178322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33165955-A-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00226 (343/152024) while in subpopulation EAS AF= 0.0103 (53/5152). AF 95% confidence interval is 0.00808. There are 2 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3 linkuse as main transcript	c.4458T>A	p.Gly1486=	synonymous_variant	62/66	ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL11A2	ENST00000341947.7 linkuse as main transcript	c.4458T>A	p.Gly1486=	synonymous_variant	62/66	5	NM_080680.3	P4
COL11A2	ENST00000374708.8 linkuse as main transcript	c.4200T>A	p.Gly1400=	synonymous_variant	60/64	5		A1
COL11A2	ENST00000683572.1 linkuse as main transcript	n.264T>A		non_coding_transcript_exon_variant	5/9
COL11A2	ENST00000477772.1 linkuse as main transcript	n.273-139T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

345

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0105

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00283

AC:

706

AN:

249318

Hom.:

AF XY:

0.00293

AC XY:

396

AN XY:

135104

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.000999

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00264

AC:

3853

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1946

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00373

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.00247

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00226

AC:

343

AN:

152024

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0103

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.000850

Gnomad4 NFE

AF:

0.00272

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00222

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 19, 2014	p.Gly1486Gly in exon 62 of COL11A2: This variant is not expected to have clinica l significance because it does not alter an amino acid residue, is not located w ithin the splice consensus sequence, and has been identified in 1.2% (103/8668) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs143186319). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2017	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. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	COL11A2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 06, 2023	- -

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

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

Fibrochondrogenesis 2

Benign:1

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

Dec 22, 2021

- -

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

-0.84

Cadd

Benign

1.1

Dann

Benign

0.71

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