rs2744507

Variant names:

• chr6-33181101-C-T
• rs2744507
• NM_080680.3:c.1179+10G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080680.3(COL11A2):​c.1179+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,992 control chromosomes in the GnomAD database, including 14,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1017 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13942 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -4.74
• Publications: 23 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-33181101-C-T is Benign according to our data. Variant chr6-33181101-C-T is described in ClinVar as Benign. ClinVar VariationId is 46554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 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.1179+10G>A		intron	N/A	NP_542411.2
	COL11A2	NM_001424108.1		c.999+10G>A		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.921+10G>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.1179+10G>A		intron	N/A	ENSP00000339915.2
	COL11A2	ENST00000930122.1		c.999+10G>A		intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.921+10G>A		intron	N/A	ENSP00000363840.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15394 AN: 152106 Hom.: 1017 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0818

GnomAD2 exomes AF: 0.121 AC: 30553 AN: 251466 AF XY: 0.127

Gnomad AFR exome AF: 0.0250

Gnomad AMR exome AF: 0.0611

Gnomad ASJ exome AF: 0.0891

Gnomad EAS exome AF: 0.0964

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.134 AC: 195662 AN: 1461768 Hom.: 13942 Cov.: 35 AF XY: 0.135 AC XY: 98345 AN XY: 727192

African (AFR) AF: 0.0236 AC: 791 AN: 33480

American (AMR) AF: 0.0616 AC: 2753 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 2372 AN: 26136

East Asian (EAS) AF: 0.112 AC: 4436 AN: 39698

South Asian (SAS) AF: 0.184 AC: 15850 AN: 86258

European-Finnish (FIN) AF: 0.177 AC: 9462 AN: 53412

Middle Eastern (MID) AF: 0.105 AC: 608 AN: 5768

European-Non Finnish (NFE) AF: 0.137 AC: 151920 AN: 1111900

Other (OTH) AF: 0.124 AC: 7470 AN: 60392

GnomAD4 genome AF: 0.101 AC: 15391 AN: 152224 Hom.: 1017 Cov.: 32 AF XY: 0.103 AC XY: 7672 AN XY: 74414

African (AFR) AF: 0.0277 AC: 1152 AN: 41542

American (AMR) AF: 0.0721 AC: 1104 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.108 AC: 558 AN: 5176

South Asian (SAS) AF: 0.182 AC: 879 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9290 AN: 68000

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.111 Hom.: 1250

Bravo AF: 0.0872

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Fibrochondrogenesis 2 (1)
-	-	1	not provided (1)
-	-	1	Otospondylomegaepiphyseal dysplasia, autosomal dominant (1)
-	-	1	Otospondylomegaepiphyseal dysplasia, autosomal recessive (1)
-	-	1	Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0060
DANN	Benign	0.63
PhyloP100		-4.7
Mutation Taster		=99/1	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: rs2744507; hg19: chr6-33148878;