rs2855453

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.4339-49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,611,724 control chromosomes in the GnomAD database, including 386,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35422 hom., cov: 29)

Exomes 𝑓: 0.69 ( 350673 hom. )

Consequence

COL11A2
NM_080680.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.753

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 6-33166615-C-A is Benign according to our data. Variant chr6-33166615-C-A is described in ClinVar as [Benign]. Clinvar id is 674799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3 link	c.4339-49G>T		intron_variant	Intron 59 of 65	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 link	c.4339-49G>T	intron_variant	Intron 59 of 65	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 link	c.4081-49G>T	intron_variant	Intron 57 of 63	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000477772.1 link	n.273-799G>T	intron_variant	Intron 5 of 8	2
COL11A2	ENST00000683572.1 link	n.234+176G>T	intron_variant	Intron 4 of 8

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

102845

AN:

151548

Hom.:

35392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.964

Gnomad SAS

AF:

0.840

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.812

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.713

GnomAD3 exomes

AF:

0.732

AC:

180080

AN:

246104

Hom.:

66992

AF XY:

0.736

AC XY:

98157

AN XY:

133332

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.781

Gnomad ASJ exome

AF:

0.834

Gnomad EAS exome

AF:

0.970

Gnomad SAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.749

GnomAD4 exome

AF:

0.689

AC:

1005966

AN:

1460058

Hom.:

350673

Cov.:

AF XY:

0.694

AC XY:

504122

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.590

Gnomad4 AMR exome

AF:

0.780

Gnomad4 ASJ exome

AF:

0.833

Gnomad4 EAS exome

AF:

0.980

Gnomad4 SAS exome

AF:

0.825

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.664

Gnomad4 OTH exome

AF:

0.712

GnomAD4 genome

AF:

0.679

AC:

102931

AN:

151666

Hom.:

35422

Cov.:

AF XY:

0.684

AC XY:

50668

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.607

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.824

Gnomad4 EAS

AF:

0.964

Gnomad4 SAS

AF:

0.841

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.669

Gnomad4 OTH

AF:

0.716

Alfa

AF:

0.693

Hom.:

32459

Bravo

AF:

0.684

Asia WGS

AF:

0.859

AC:

2987

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

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

-0.82

CADD

Benign

4.7

DANN

Benign

0.74

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