rs9368758

Positions:

• chr6-33170244-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.3582+82C>T		intron_variant		ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.3582+82C>T		intron_variant		5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.3324+82C>T		intron_variant		5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.273-4428C>T		intron_variant		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

Gnomad4 AFR exome AF: 0.0935

Gnomad4 AMR exome AF: 0.0781

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.0793

Gnomad4 FIN exome AF: 0.0766

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0924

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

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.0875

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0839 Hom.: 1861

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs9368758; hg19: chr6-33138021; COSMIC: COSV59504596;