NM_080680.3:c.2682+26A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 13
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
nonsyndromic genetic hearing loss
Inheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
otospondylomegaepiphyseal dysplasia, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive nonsyndromic hearing loss 53
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
otospondylomegaepiphyseal dysplasia
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
otospondylomegaepiphyseal dysplasia, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
fibrochondrogenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL11A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.605

AC:

147119

AN:

243214

AF XY:

0.603

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 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

African (AFR)

AF:

0.618

AC:

20624

AN:

33390

American (AMR)

AF:

0.682

AC:

30507

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

17583

AN:

26100

East Asian (EAS)

AF:

0.833

AC:

33061

AN:

39680

South Asian (SAS)

AF:

0.630

AC:

54260

AN:

86158

European-Finnish (FIN)

AF:

0.515

AC:

26913

AN:

52210

Middle Eastern (MID)

AF:

0.646

AC:

3718

AN:

5756

European-Non Finnish (NFE)

AF:

0.545

AC:

602857

AN:

1106696

Other (OTH)

AF:

0.569

AC:

34288

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.424

Heterozygous variant carriers

19479

38959

58438

77918

97397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17106

34212

51318

68424

85530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.586

AC:

88542

AN:

151186

Hom.:

26226

Cov.:

AF XY:

0.586

AC XY:

43246

AN XY:

73808

show subpopulations

African (AFR)

AF:

0.598

AC:

24555

AN:

41096

American (AMR)

AF:

0.643

AC:

9779

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2338

AN:

3458

East Asian (EAS)

AF:

0.791

AC:

4027

AN:

5088

South Asian (SAS)

AF:

0.636

AC:

3042

AN:

4786

European-Finnish (FIN)

AF:

0.523

AC:

5477

AN:

10468

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37355

AN:

67778

Other (OTH)

AF:

0.612

AC:

1282

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1706

3412

5117

6823

8529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.571

Hom.:

103792

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

(source)

DANN

Benign

0.52

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over