rs9368758

Variant names:

• chr6-33170244-G-A
• rs9368758
• NM_080680.3:c.3582+82C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33170244-G-A
• chr6-33170244-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080680.3(COL11A2):​c.3582+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,570,954 control chromosomes in the GnomAD database, including 10,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (1222 hom., cov: 31)
  • Exomes 𝑓: 0.086 (9321 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.506
• Publications: 32 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-33170244-G-A is Benign according to our data. Variant chr6-33170244-G-A is described in ClinVar as Benign. ClinVar VariationId is 1235794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.3582+82C>T		intron_variant	Intron 48 of 65	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.3582+82C>T		intron_variant	Intron 48 of 65	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.3324+82C>T		intron_variant	Intron 46 of 63	5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.273-4428C>T		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14424 AN: 152084 Hom.: 1211 Cov.: 31

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0856 AC: 121487 AN: 1418752 Hom.: 9321 Cov.: 29 AF XY: 0.0846 AC XY: 59845 AN XY: 707006

African (AFR) AF: 0.0935 AC: 3030 AN: 32422

American (AMR) AF: 0.0781 AC: 3317 AN: 42476

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 1199 AN: 25700

East Asian (EAS) AF: 0.523 AC: 20303 AN: 38786

South Asian (SAS) AF: 0.0793 AC: 6690 AN: 84354

European-Finnish (FIN) AF: 0.0766 AC: 4001 AN: 52216

Middle Eastern (MID) AF: 0.0709 AC: 405 AN: 5716

European-Non Finnish (NFE) AF: 0.0715 AC: 77103 AN: 1078188

Other (OTH) AF: 0.0924 AC: 5439 AN: 58894

GnomAD4 genome AF: 0.0949 AC: 14442 AN: 152202 Hom.: 1222 Cov.: 31 AF XY: 0.0968 AC XY: 7201 AN XY: 74404

African (AFR) AF: 0.0966 AC: 4009 AN: 41500

American (AMR) AF: 0.0840 AC: 1286 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2629 AN: 5154

South Asian (SAS) AF: 0.0875 AC: 422 AN: 4824

European-Finnish (FIN) AF: 0.0851 AC: 903 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4708 AN: 68020

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.0839 Hom.: 4018

Bravo AF: 0.0993

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.63
PhyloP100		-0.51
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: rs9368758; hg19: chr6-33138021; COSMIC: COSV59504596;