rs1799908

Variant names:

• chr6-33176466-T-A
• rs1799908
• NM_080680.3:c.2136A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33176466-T-A
• chr6-33176466-T-G
• chr6-33176466-T-C

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.2136A>T​(p.Gly712Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,610,068 control chromosomes in the GnomAD database, including 155,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G712G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.47 (17184 hom., cov: 30)
  • Exomes 𝑓: 0.43 (138701 hom.)
• Consequence: COL11A2 NM_080680.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:17
• Conservation: PhyloP100: 0.197
• Publications: 48 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=-0.5).
• BP6: Variant 6-33176466-T-A is Benign according to our data. Variant chr6-33176466-T-A is described in ClinVar as Benign. ClinVar VariationId is 46558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.197 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 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.2136A>T	p.Gly712Gly	synonymous	Exon 27 of 66	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.1956A>T	p.Gly652Gly	synonymous	Exon 26 of 65	NP_001411037.1
	COL11A2	NM_080681.3		c.1878A>T	p.Gly626Gly	synonymous	Exon 25 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.2136A>T	p.Gly712Gly	synonymous	Exon 27 of 66	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.1956A>T	p.Gly652Gly	synonymous	Exon 26 of 65	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.1878A>T	p.Gly626Gly	synonymous	Exon 25 of 64	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70966 AN: 151620 Hom.: 17155 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.474

GnomAD2 exomes AF: 0.485 AC: 119248 AN: 245818 AF XY: 0.477

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.739

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.429 AC: 625325 AN: 1458330 Hom.: 138701 Cov.: 45 AF XY: 0.430 AC XY: 312167 AN XY: 725548

African (AFR) AF: 0.497 AC: 16605 AN: 33436

American (AMR) AF: 0.594 AC: 26523 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 11405 AN: 26112

East Asian (EAS) AF: 0.752 AC: 29830 AN: 39674

South Asian (SAS) AF: 0.502 AC: 43263 AN: 86120

European-Finnish (FIN) AF: 0.482 AC: 25154 AN: 52232

Middle Eastern (MID) AF: 0.457 AC: 2586 AN: 5660

European-Non Finnish (NFE) AF: 0.399 AC: 442926 AN: 1110200

Other (OTH) AF: 0.449 AC: 27033 AN: 60252

GnomAD4 genome AF: 0.468 AC: 71048 AN: 151738 Hom.: 17184 Cov.: 30 AF XY: 0.475 AC XY: 35190 AN XY: 74100

African (AFR) AF: 0.512 AC: 21152 AN: 41348

American (AMR) AF: 0.520 AC: 7931 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3464

East Asian (EAS) AF: 0.747 AC: 3846 AN: 5148

South Asian (SAS) AF: 0.522 AC: 2505 AN: 4796

European-Finnish (FIN) AF: 0.505 AC: 5313 AN: 10522

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27499 AN: 67878

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.419 Hom.: 10435

Bravo AF: 0.476

Asia WGS AF: 0.572 AC: 1988 AN: 3478

EpiCase AF: 0.417

EpiControl AF: 0.410

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	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	-0.50
CADD	Benign	9.4
DANN	Benign	0.76
PhyloP100		0.20
Mutation Taster		=92/8	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: rs1799908; hg19: chr6-33144243; COSMIC: COSV59497779; COSMIC: COSV59497779;