rs1799910

Variant names:

• chr6-33171551-C-T
• rs1799910
• NM_080680.3:c.3174G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33171551-C-T
• chr6-33171551-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080680.3(COL11A2):​c.3174G>A​(p.Pro1058Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,613,278 control chromosomes in the GnomAD database, including 177,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19822 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158000 hom.)
• Consequence: COL11A2 NM_080680.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: -4.29
• Publications: 46 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 6-33171551-C-T is Benign according to our data. Variant chr6-33171551-C-T is described in ClinVar as Benign. ClinVar VariationId is 46565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 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.3174G>A	p.Pro1058Pro	synonymous	Exon 43 of 66	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.2994G>A	p.Pro998Pro	synonymous	Exon 42 of 65	NP_001411037.1
	COL11A2	NM_080681.3		c.2916G>A	p.Pro972Pro	synonymous	Exon 41 of 64	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.3174G>A	p.Pro1058Pro	synonymous	Exon 43 of 66	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.2994G>A	p.Pro998Pro	synonymous	Exon 42 of 65	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.2916G>A	p.Pro972Pro	synonymous	Exon 41 of 64	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75873 AN: 151884 Hom.: 19786 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.486

GnomAD2 exomes AF: 0.449 AC: 112395 AN: 250226 AF XY: 0.459

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.333

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.460 AC: 672638 AN: 1461276 Hom.: 158000 Cov.: 58 AF XY: 0.464 AC XY: 337381 AN XY: 726946

African (AFR) AF: 0.669 AC: 22386 AN: 33472

American (AMR) AF: 0.306 AC: 13662 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 13151 AN: 26130

East Asian (EAS) AF: 0.343 AC: 13600 AN: 39690

South Asian (SAS) AF: 0.585 AC: 50403 AN: 86226

European-Finnish (FIN) AF: 0.396 AC: 21141 AN: 53340

Middle Eastern (MID) AF: 0.533 AC: 3077 AN: 5768

European-Non Finnish (NFE) AF: 0.456 AC: 506998 AN: 1111584

Other (OTH) AF: 0.467 AC: 28220 AN: 60378

GnomAD4 genome AF: 0.500 AC: 75951 AN: 152002 Hom.: 19822 Cov.: 32 AF XY: 0.495 AC XY: 36771 AN XY: 74290

African (AFR) AF: 0.650 AC: 26961 AN: 41486

American (AMR) AF: 0.395 AC: 6032 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1718 AN: 5142

South Asian (SAS) AF: 0.578 AC: 2785 AN: 4816

European-Finnish (FIN) AF: 0.384 AC: 4060 AN: 10576

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31076 AN: 67904

Other (OTH) AF: 0.484 AC: 1023 AN: 2114

Alfa AF: 0.474 Hom.: 44954

Bravo AF: 0.500

Asia WGS AF: 0.475 AC: 1652 AN: 3478

EpiCase AF: 0.454

EpiControl AF: 0.463

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Fibrochondrogenesis 2 (2)
-	-	2	Otospondylomegaepiphyseal dysplasia, autosomal dominant (2)
-	-	2	Otospondylomegaepiphyseal dysplasia, autosomal recessive (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 13 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 53 (1)
-	-	1	not provided (1)
-	-	1	Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.31
DANN	Benign	0.49
PhyloP100		-4.3
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: rs1799910; hg19: chr6-33139328; COSMIC: COSV59500329;