rs55730247

Variant names:

• chr6-33174151-AC-A
• rs55730247
• NM_080680.3:c.2484+13delG

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_080680.3(COL11A2):​c.2484+13delG 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
• Publications: 5 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, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• otospondylomegaepiphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 53

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• otospondylomegaepiphyseal dysplasia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• otospondylomegaepiphyseal dysplasia, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -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 VariationId is 262308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 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.2484+13delG		intron	N/A	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.2304+13delG		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.2226+13delG		intron	N/A	NP_542412.2	Q4VXY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.2484+13delG		intron	N/A	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.2304+13delG		intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.2226+13delG		intron	N/A	ENSP00000363840.4	Q4VXY6

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

GnomAD2 exomes AF: 0.105 AC: 21532 AN: 204660 AF XY: 0.102

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 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

African (AFR) AF: 0.0945 AC: 3063 AN: 32420

American (AMR) AF: 0.0781 AC: 3308 AN: 42336

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 1194 AN: 25570

East Asian (EAS) AF: 0.522 AC: 19730 AN: 37814

South Asian (SAS) AF: 0.0798 AC: 6571 AN: 82362

European-Finnish (FIN) AF: 0.0767 AC: 3894 AN: 50766

Middle Eastern (MID) AF: 0.0706 AC: 403 AN: 5706

European-Non Finnish (NFE) AF: 0.0725 AC: 79280 AN: 1093898

Other (OTH) AF: 0.0933 AC: 5522 AN: 59176

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

African (AFR) AF: 0.101 AC: 4010 AN: 39528

American (AMR) AF: 0.0866 AC: 1286 AN: 14848

Ashkenazi Jewish (ASJ) AF: 0.0442 AC: 150 AN: 3394

East Asian (EAS) AF: 0.516 AC: 2599 AN: 5036

South Asian (SAS) AF: 0.0932 AC: 425 AN: 4562

European-Finnish (FIN) AF: 0.0891 AC: 900 AN: 10100

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0710 AC: 4715 AN: 66364

Other (OTH) AF: 0.122 AC: 251 AN: 2050

Alfa AF: 0.0718 Hom.: 80

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Fibrochondrogenesis 1 (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
PhyloP100		-1.5
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: rs55730247; hg19: chr6-33141928; COSMIC: COSV107403544; COSMIC: COSV107403544;