rs2269346

Variant names:

• chr6-33191121-C-T
• rs2269346
• NM_080680.3:c.82+1038G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080680.3(COL11A2):​c.82+1038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,214 control chromosomes in the GnomAD database, including 1,216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.093 (1216 hom., cov: 32)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 24 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080680.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	NM_080680.3	MANE Select	c.82+1038G>A		intron	N/A	NP_542411.2
	COL11A2	NM_001424108.1		c.82+1038G>A		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.82+1038G>A		intron	N/A	NP_542412.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.82+1038G>A		intron	N/A	ENSP00000339915.2
	COL11A2	ENST00000395194.1	TSL:1	c.82+1038G>A		intron	N/A	ENSP00000378620.1
	COL11A2	ENST00000374708.8	TSL:5	c.82+1038G>A		intron	N/A	ENSP00000363840.4

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14178 AN: 152096 Hom.: 1205 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0933 AC: 14196 AN: 152214 Hom.: 1216 Cov.: 32 AF XY: 0.0951 AC XY: 7075 AN XY: 74410

African (AFR) AF: 0.0904 AC: 3757 AN: 41546

American (AMR) AF: 0.0830 AC: 1269 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3468

East Asian (EAS) AF: 0.515 AC: 2652 AN: 5154

South Asian (SAS) AF: 0.0880 AC: 424 AN: 4816

European-Finnish (FIN) AF: 0.0849 AC: 900 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4711 AN: 68016

Other (OTH) AF: 0.119 AC: 252 AN: 2110

Alfa AF: 0.0819 Hom.: 3677

Bravo AF: 0.0973

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.50
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269346; hg19: chr6-33158898;