rs55730247

Positions:

• chr6-33174151-AC-A
• chr6-33174151-AC-ACC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_080680.3(COL11A2):​c.2484+13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,577,118 control chromosomes in the GnomAD database, including 10,475 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (1219 hom., cov: 30)
  • Exomes 𝑓: 0.086 (9256 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.49

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-33174151-AC-A is Benign according to our data. Variant chr6-33174151-AC-A is described in ClinVar as [Benign]. Clinvar id is 262308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-33174151-AC-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.2484+13del		intron_variant		ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.2484+13del		intron_variant		5	NM_080680.3	ENSP00000339915	P4
COL11A2	ENST00000361917.6	c.1057+13del		intron_variant		5		ENSP00000355123
COL11A2	ENST00000374708.8	c.2226+13del		intron_variant		5		ENSP00000363840	A1
COL11A2	ENST00000477772.1	n.272+2857del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14398 AN: 146962 Hom.: 1208 Cov.: 30

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0536

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0442

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.105 AC: 21532 AN: 204660 Hom.: 2546 AF XY: 0.102 AC XY: 11408 AN XY: 111414

Gnomad AFR exome AF: 0.0960

Gnomad AMR exome AF: 0.0762

Gnomad ASJ exome AF: 0.0450

Gnomad EAS exome AF: 0.518

Gnomad SAS exome AF: 0.0768

Gnomad FIN exome AF: 0.0781

Gnomad NFE exome AF: 0.0679

Gnomad OTH exome AF: 0.0859

GnomAD4 exome AF: 0.0860 AC: 122965 AN: 1430048 Hom.: 9256 Cov.: 37 AF XY: 0.0850 AC XY: 60306 AN XY: 709532

Gnomad4 AFR exome AF: 0.0945

Gnomad4 AMR exome AF: 0.0781

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.0798

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.0725

Gnomad4 OTH exome AF: 0.0933

GnomAD4 genome AF: 0.0980 AC: 14416 AN: 147070 Hom.: 1219 Cov.: 30 AF XY: 0.100 AC XY: 7194 AN XY: 71734

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.0442

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.0932

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0718 Hom.: 80

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 08, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

Jun 14, 2016

- -

Fibrochondrogenesis 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Stickler Syndrome, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs55730247; hg19: chr6-33141928;