rs986521

Variant names:

• chr6-33168368-G-A
• rs986521
• NM_080680.3:c.3960+151C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33168368-G-A
• chr6-33168368-G-C
• chr6-33168368-G-T

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.3960+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 861,220 control chromosomes in the GnomAD database, including 272,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (50770 hom., cov: 28)
  • Exomes 𝑓: 0.78 (221899 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 30 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=-0.96).
• BP6: Variant 6-33168368-G-A is Benign according to our data. Variant chr6-33168368-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.3960+151C>T		intron_variant	Intron 54 of 65	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.3960+151C>T		intron_variant	Intron 54 of 65	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.3702+151C>T		intron_variant	Intron 52 of 63	5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.273-2552C>T		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 122605 AN: 150106 Hom.: 50716 Cov.: 28

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.913

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.784 AC: 557761 AN: 710996 Hom.: 221899 AF XY: 0.790 AC XY: 296733 AN XY: 375778

African (AFR) AF: 0.933 AC: 17228 AN: 18460

American (AMR) AF: 0.832 AC: 30333 AN: 36444

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 18442 AN: 21084

East Asian (EAS) AF: 0.992 AC: 32837 AN: 33094

South Asian (SAS) AF: 0.902 AC: 60442 AN: 67006

European-Finnish (FIN) AF: 0.711 AC: 31618 AN: 44490

Middle Eastern (MID) AF: 0.909 AC: 2528 AN: 2782

European-Non Finnish (NFE) AF: 0.743 AC: 335845 AN: 452098

Other (OTH) AF: 0.802 AC: 28488 AN: 35538

GnomAD4 genome AF: 0.817 AC: 122716 AN: 150224 Hom.: 50770 Cov.: 28 AF XY: 0.818 AC XY: 60059 AN XY: 73438

African (AFR) AF: 0.929 AC: 38108 AN: 41008

American (AMR) AF: 0.827 AC: 12466 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 2984 AN: 3446

East Asian (EAS) AF: 0.983 AC: 5011 AN: 5100

South Asian (SAS) AF: 0.911 AC: 4324 AN: 4748

European-Finnish (FIN) AF: 0.710 AC: 7384 AN: 10406

Middle Eastern (MID) AF: 0.906 AC: 261 AN: 288

European-Non Finnish (NFE) AF: 0.742 AC: 49853 AN: 67174

Other (OTH) AF: 0.850 AC: 1772 AN: 2084

Alfa AF: 0.784 Hom.: 136938

Bravo AF: 0.838

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 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	-0.96
CADD	Benign	0.59
DANN	Benign	0.40
PhyloP100		-1.4
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: rs986521; hg19: chr6-33136145;