rs2855425

Variant names:

• chr6-33176596-G-A
• rs2855425
• NM_080680.3:c.2116-110C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33176596-G-A
• chr6-33176596-G-C
• chr6-33176596-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.2116-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,396,414 control chromosomes in the GnomAD database, including 391,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (47196 hom., cov: 31)
  • Exomes 𝑓: 0.74 (344193 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.491
• 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=-0.84).
• BP6: Variant 6-33176596-G-A is Benign according to our data. Variant chr6-33176596-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 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.2116-110C>T		intron	N/A	NP_542411.2
	COL11A2	NM_001424108.1		c.1936-110C>T		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.1858-110C>T		intron	N/A	NP_542412.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.2116-110C>T		intron	N/A	ENSP00000339915.2
	COL11A2	ENST00000930122.1		c.1936-110C>T		intron	N/A	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.1858-110C>T		intron	N/A	ENSP00000363840.4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119019 AN: 151918 Hom.: 47152 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.740 AC: 920888 AN: 1244378 Hom.: 344193 Cov.: 17 AF XY: 0.745 AC XY: 466368 AN XY: 626102

African (AFR) AF: 0.881 AC: 25310 AN: 28716

American (AMR) AF: 0.799 AC: 31350 AN: 39234

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 19697 AN: 24292

East Asian (EAS) AF: 0.983 AC: 37483 AN: 38132

South Asian (SAS) AF: 0.889 AC: 70571 AN: 79390

European-Finnish (FIN) AF: 0.700 AC: 36410 AN: 52016

Middle Eastern (MID) AF: 0.831 AC: 4443 AN: 5348

European-Non Finnish (NFE) AF: 0.709 AC: 655409 AN: 924326

Other (OTH) AF: 0.760 AC: 40215 AN: 52924

GnomAD4 genome AF: 0.783 AC: 119119 AN: 152036 Hom.: 47196 Cov.: 31 AF XY: 0.785 AC XY: 58311 AN XY: 74300

African (AFR) AF: 0.872 AC: 36178 AN: 41470

American (AMR) AF: 0.788 AC: 12043 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2779 AN: 3470

East Asian (EAS) AF: 0.972 AC: 5016 AN: 5160

South Asian (SAS) AF: 0.905 AC: 4362 AN: 4820

European-Finnish (FIN) AF: 0.708 AC: 7485 AN: 10574

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48760 AN: 67938

Other (OTH) AF: 0.800 AC: 1689 AN: 2110

Alfa AF: 0.747 Hom.: 179211

Bravo AF: 0.794

Asia WGS AF: 0.901 AC: 3132 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-0.49
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: rs2855425; hg19: chr6-33144373;