rs151098305

Variant names:

• chr6-33169482-G-A
• rs151098305
• NM_080680.3:c.3699C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33169482-G-A
• chr6-33169482-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_080680.3(COL11A2):​c.3699C>T​(p.Arg1233Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,612,660 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (87 hom.)
• Consequence: COL11A2 NM_080680.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.57
• Publications: 1 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=-0.9).
• BP6: Variant 6-33169482-G-A is Benign according to our data. Variant chr6-33169482-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00164 (249/152214) while in subpopulation SAS AF = 0.0334 (161/4814). AF 95% confidence interval is 0.0292. There are 6 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

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.3699C>T	p.Arg1233Arg	synonymous	Exon 51 of 66	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.3519C>T	p.Arg1173Arg	synonymous	Exon 50 of 65	NP_001411037.1
	COL11A2	NM_080681.3		c.3441C>T	p.Arg1147Arg	synonymous	Exon 49 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.3699C>T	p.Arg1233Arg	synonymous	Exon 51 of 66	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.3519C>T	p.Arg1173Arg	synonymous	Exon 50 of 65	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.3441C>T	p.Arg1147Arg	synonymous	Exon 49 of 64	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152096 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00440 AC: 1085 AN: 246332 AF XY: 0.00591

Gnomad AFR exome AF: 0.00106

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00235

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000217

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00231 AC: 3373 AN: 1460446 Hom.: 87 Cov.: 33 AF XY: 0.00329 AC XY: 2389 AN XY: 726558

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26134

East Asian (EAS) AF: 0.00161 AC: 64 AN: 39700

South Asian (SAS) AF: 0.0326 AC: 2810 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52142

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1111876

Other (OTH) AF: 0.00467 AC: 282 AN: 60380

GnomAD4 genome AF: 0.00164 AC: 249 AN: 152214 Hom.: 6 Cov.: 31 AF XY: 0.00219 AC XY: 163 AN XY: 74436

African (AFR) AF: 0.000987 AC: 41 AN: 41522

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3466

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5172

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000410 Hom.: 0

Bravo AF: 0.000722

Asia WGS AF: 0.0230 AC: 79 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Connective tissue disorder (1)
-	-	1	Fibrochondrogenesis 2 (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	-0.90
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.6
Mutation Taster		=98/2	polymorphism

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: rs151098305; hg19: chr6-33137259;