rs2076311

Variant names:

• chr6-33177592-C-A
• rs2076311
• NM_080680.3:c.1917+70G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33177592-C-A
• chr6-33177592-C-G
• chr6-33177592-C-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.1917+70G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,595,442 control chromosomes in the GnomAD database, including 79,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7753 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71428 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 29 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=-0.86).
• BP6: Variant 6-33177592-C-A is Benign according to our data. Variant chr6-33177592-C-A is described in ClinVar as Benign. ClinVar VariationId is 674972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.1917+70G>T		intron_variant	Intron 22 of 65	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.1917+70G>T		intron_variant	Intron 22 of 65	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.1659+70G>T		intron_variant	Intron 20 of 63	5		ENSP00000363840.4
COL11A2	ENST00000361917.6	c.489+70G>T		intron_variant	Intron 9 of 23	5		ENSP00000355123.2
COL11A2	ENST00000477772.1	n.136+70G>T		intron_variant	Intron 2 of 8	2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47900 AN: 151842 Hom.: 7750 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.311 AC: 448969 AN: 1443482 Hom.: 71428 Cov.: 29 AF XY: 0.314 AC XY: 225792 AN XY: 718452

African (AFR) AF: 0.387 AC: 12834 AN: 33142

American (AMR) AF: 0.208 AC: 9210 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9706 AN: 25950

East Asian (EAS) AF: 0.231 AC: 9106 AN: 39476

South Asian (SAS) AF: 0.387 AC: 33184 AN: 85768

European-Finnish (FIN) AF: 0.220 AC: 11427 AN: 52014

Middle Eastern (MID) AF: 0.374 AC: 2147 AN: 5734

European-Non Finnish (NFE) AF: 0.312 AC: 342716 AN: 1097350

Other (OTH) AF: 0.312 AC: 18639 AN: 59776

GnomAD4 genome AF: 0.315 AC: 47918 AN: 151960 Hom.: 7753 Cov.: 32 AF XY: 0.310 AC XY: 23008 AN XY: 74276

African (AFR) AF: 0.361 AC: 14945 AN: 41416

American (AMR) AF: 0.268 AC: 4104 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1151 AN: 5142

South Asian (SAS) AF: 0.382 AC: 1841 AN: 4814

European-Finnish (FIN) AF: 0.204 AC: 2163 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21241 AN: 67944

Other (OTH) AF: 0.323 AC: 678 AN: 2100

Alfa AF: 0.314 Hom.: 28408

Bravo AF: 0.318

Asia WGS AF: 0.327 AC: 1140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.58
PhyloP100		-1.0
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: rs2076311; hg19: chr6-33145369; COSMIC: COSV107403521; COSMIC: COSV107403521;