rs2855438

Variant names:

• chr6-33171062-A-T
• rs2855438
• NM_080680.3:c.3366+52T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080680.3(COL11A2):​c.3366+52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,573,624 control chromosomes in the GnomAD database, including 16,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1884 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14964 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.668
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-33171062-A-T is Benign according to our data. Variant chr6-33171062-A-T is described in ClinVar as Benign. ClinVar VariationId is 1229410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	NM_080680.3	MANE Select	c.3366+52T>A		intron	N/A	NP_542411.2
	COL11A2	NM_001424108.1		c.3186+52T>A		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.3108+52T>A		intron	N/A	NP_542412.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.3366+52T>A		intron	N/A	ENSP00000339915.2
	COL11A2	ENST00000930122.1		c.3186+52T>A		intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.3108+52T>A		intron	N/A	ENSP00000363840.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23061 AN: 151986 Hom.: 1871 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.142 AC: 201845 AN: 1421520 Hom.: 14964 Cov.: 33 AF XY: 0.143 AC XY: 100682 AN XY: 704040

African (AFR) AF: 0.186 AC: 6036 AN: 32454

American (AMR) AF: 0.0836 AC: 3182 AN: 38068

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 2441 AN: 25516

East Asian (EAS) AF: 0.113 AC: 4237 AN: 37420

South Asian (SAS) AF: 0.196 AC: 16197 AN: 82812

European-Finnish (FIN) AF: 0.176 AC: 8920 AN: 50656

Middle Eastern (MID) AF: 0.136 AC: 761 AN: 5590

European-Non Finnish (NFE) AF: 0.139 AC: 151773 AN: 1090098

Other (OTH) AF: 0.141 AC: 8298 AN: 58906

GnomAD4 genome AF: 0.152 AC: 23115 AN: 152104 Hom.: 1884 Cov.: 33 AF XY: 0.153 AC XY: 11386 AN XY: 74352

African (AFR) AF: 0.193 AC: 8020 AN: 41470

American (AMR) AF: 0.101 AC: 1546 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3468

East Asian (EAS) AF: 0.108 AC: 556 AN: 5156

South Asian (SAS) AF: 0.193 AC: 930 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9516 AN: 67976

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.144 Hom.: 187

Bravo AF: 0.146

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.67
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: rs2855438; hg19: chr6-33138839;