6-33173476-T-G

Variant names:

Variant summary

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

The NM_080680.3(COL11A2):c.2682+26A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,606,098 control chromosomes in the GnomAD database, including 263,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26226 hom., cov: 28)

Exomes 𝑓: 0.57 ( 236985 hom. )

Consequence

COL11A2
NM_080680.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.02

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=-0.86).

BP6

Variant 6-33173476-T-G is Benign according to our data. Variant chr6-33173476-T-G is described in ClinVar as [Benign]. Clinvar id is 262310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3 link	c.2682+26A>C		intron_variant	Intron 36 of 65	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 link	c.2682+26A>C	intron_variant	Intron 36 of 65	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 link	c.2424+26A>C	intron_variant	Intron 34 of 63	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000361917.6 link	c.1254+26A>C	intron_variant	Intron 23 of 23	5		ENSP00000355123.2	H0YIS1
COL11A2	ENST00000477772.1 link	n.272+3533A>C	intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

88501

AN:

151072

Hom.:

26214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.791

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.605

AC:

147119

AN:

243214

Hom.:

45579

AF XY:

0.603

AC XY:

79661

AN XY:

132154

show subpopulations

Gnomad AFR exome

AF:

0.600

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.677

Gnomad EAS exome

AF:

0.810

Gnomad SAS exome

AF:

0.631

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.593

GnomAD4 exome

AF:

0.566

AC:

823811

AN:

1454912

Hom.:

236985

Cov.:

AF XY:

0.569

AC XY:

411842

AN XY:

724030

show subpopulations

Gnomad4 AFR exome

AF:

0.618

Gnomad4 AMR exome

AF:

0.682

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.630

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.586

AC:

88542

AN:

151186

Hom.:

26226

Cov.:

AF XY:

0.586

AC XY:

43246

AN XY:

73808

show subpopulations

Gnomad4 AFR

AF:

0.598

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.676

Gnomad4 EAS

AF:

0.791

Gnomad4 SAS

AF:

0.636

Gnomad4 FIN

AF:

0.523

Gnomad4 NFE

AF:

0.551

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.573

Hom.:

47185

Bravo

AF:

0.596

Asia WGS

AF:

0.677

AC:

2356

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Otospondylomegaepiphyseal dysplasia, autosomal dominant

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

Otospondylomegaepiphyseal dysplasia, autosomal recessive

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 13, 2018

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. -

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

- -

Fibrochondrogenesis 2

Benign:1

Jul 22, 2021

Genome-Nilou Lab

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

-0.86

CADD

Benign

0.015

DANN

Benign

0.52

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