rs2744507

Positions:

chr6-33181101-C-T

Variant summary

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

The NM_080680.3(COL11A2):c.1179+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,992 control chromosomes in the GnomAD database, including 14,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1017 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13942 hom. )

Consequence

COL11A2
NM_080680.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -4.74

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=-0.88).

BP6

Variant 6-33181101-C-T is Benign according to our data. Variant chr6-33181101-C-T is described in ClinVar as [Benign]. Clinvar id is 46554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33181101-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3 linkuse as main transcript	c.1179+10G>A		intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A2	ENST00000341947.7 linkuse as main transcript	c.1179+10G>A		intron_variant		5	NM_080680.3	P4
COL11A2	ENST00000374708.8 linkuse as main transcript	c.921+10G>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15394

AN:

152106

Hom.:

1017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0795

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.0818

GnomAD3 exomes

AF:

0.121

AC:

30553

AN:

251466

Hom.:

2199

AF XY:

0.127

AC XY:

17318

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0611

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.0964

Gnomad SAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.134

AC:

195662

AN:

1461768

Hom.:

13942

Cov.:

AF XY:

0.135

AC XY:

98345

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.0616

Gnomad4 ASJ exome

AF:

0.0908

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.101

AC:

15391

AN:

152224

Hom.:

1017

Cov.:

AF XY:

0.103

AC XY:

7672

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.0721

Gnomad4 ASJ

AF:

0.0795

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.0829

Alfa

AF:

0.111

Hom.:

739

Bravo

AF:

0.0872

Asia WGS

AF:

0.115

AC:

398

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 2016	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. -
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	May 07, 2012	1179+10G>A in Intron 09 of COL11A2: This variant is not expected to have clinica l significance because it is not located within the conserved splice consensus s equence and has been identified in 13.0% (914/7020) of European American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs2744507). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Otospondylomegaepiphyseal dysplasia, autosomal dominant

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Stickler Syndrome, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Fibrochondrogenesis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0060

DANN

Benign

0.63

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