NM_080680.3:c.2214+88G>C

Variant names:

• chr6-33176171-C-G
• rs2254287
• NM_080680.3:c.2214+88G>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.2214+88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,602,926 control chromosomes in the GnomAD database, including 155,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17233 hom., cov: 31)
  • Exomes 𝑓: 0.43 (138284 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.470
• Publications: 57 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 6-33176171-C-G is Benign according to our data. Variant chr6-33176171-C-G is described in ClinVar as Benign. ClinVar VariationId is 674768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

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.2214+88G>C		intron	N/A	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.2034+88G>C		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.1956+88G>C		intron	N/A	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.2214+88G>C		intron	N/A	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.2034+88G>C		intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.1956+88G>C		intron	N/A	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71106 AN: 151726 Hom.: 17204 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.429 AC: 623104 AN: 1451082 Hom.: 138284 Cov.: 32 AF XY: 0.431 AC XY: 311285 AN XY: 722512

African (AFR) AF: 0.499 AC: 16618 AN: 33282

American (AMR) AF: 0.595 AC: 26478 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 11399 AN: 26070

East Asian (EAS) AF: 0.752 AC: 29790 AN: 39620

South Asian (SAS) AF: 0.503 AC: 43285 AN: 86042

European-Finnish (FIN) AF: 0.482 AC: 25244 AN: 52368

Middle Eastern (MID) AF: 0.456 AC: 2618 AN: 5738

European-Non Finnish (NFE) AF: 0.399 AC: 440683 AN: 1103360

Other (OTH) AF: 0.449 AC: 26989 AN: 60068

GnomAD4 genome AF: 0.469 AC: 71188 AN: 151844 Hom.: 17233 Cov.: 31 AF XY: 0.475 AC XY: 35287 AN XY: 74212

African (AFR) AF: 0.514 AC: 21243 AN: 41358

American (AMR) AF: 0.520 AC: 7939 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1466 AN: 3468

East Asian (EAS) AF: 0.747 AC: 3851 AN: 5158

South Asian (SAS) AF: 0.522 AC: 2518 AN: 4824

European-Finnish (FIN) AF: 0.505 AC: 5313 AN: 10530

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.405 AC: 27528 AN: 67924

Other (OTH) AF: 0.477 AC: 1005 AN: 2108

Alfa AF: 0.274 Hom.: 640

Bravo AF: 0.477

Asia WGS AF: 0.573 AC: 1990 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.47
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: rs2254287; hg19: chr6-33143948; COSMIC: COSV59495852; COSMIC: COSV59495852;