rs555657704

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_080680.3(COL11A2):c.2584-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,594,094 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

COL11A2
NM_080680.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.994

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 -16 ACMG points.

BP6

Variant 6-33173749-TG-T is Benign according to our data. Variant chr6-33173749-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 227266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33173749-TG-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00106 (160/151480) while in subpopulation NFE AF= 0.00196 (133/67788). AF 95% confidence interval is 0.00169. There are 1 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome 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.2584-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL11A2	ENST00000341947.7 linkuse as main transcript	c.2584-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_080680.3	P4
COL11A2	ENST00000361917.6 linkuse as main transcript	c.1157-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5
COL11A2	ENST00000374708.8 linkuse as main transcript	c.2326-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		A1
COL11A2	ENST00000477772.1 linkuse as main transcript	n.272+3259del	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

160

AN:

151362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000760

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00124

AC:

298

AN:

239644

Hom.:

AF XY:

0.00134

AC XY:

174

AN XY:

129382

show subpopulations

Gnomad AFR exome

AF:

0.000382

Gnomad AMR exome

AF:

0.000327

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000394

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.00258

GnomAD4 exome

AF:

0.00148

AC:

2141

AN:

1442614

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1023

AN XY:

714712

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000458

Gnomad4 ASJ exome

AF:

0.000441

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.000322

Gnomad4 FIN exome

AF:

0.00127

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00106

AC:

160

AN:

151480

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74034

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.000760

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	COL11A2: BP4, BS2 -

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 26, 2017	c.2584-5delC in intron 34 of COL11A2: This variant is not expected to have clin ical significance because this variant has been identified in 0.21% (254/121798) of European chromosomes including 2 homozygotes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs555657704). Furthermore, computational tools do not predict an impact to splicing. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 28, 2016	- -

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Fibrochondrogenesis 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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