rs2855459

Variant names:

• chr6-33186879-G-A
• rs2855459
• NM_080680.3:c.607-61C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33186879-G-A
• chr6-33186879-G-C
• chr6-33186879-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.607-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,607,328 control chromosomes in the GnomAD database, including 14,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1015 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13810 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329
• Publications: 34 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

ENSG00000305994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-33186879-G-A is Benign according to our data. Variant chr6-33186879-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	NM_080680.3	MANE Select	c.607-61C>T		intron	N/A	NP_542411.2
	COL11A2	NM_001424108.1		c.607-61C>T		intron	N/A	NP_001411037.1
	COL11A2	NM_080681.3		c.607-61C>T		intron	N/A	NP_542412.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.607-61C>T		intron	N/A	ENSP00000339915.2
	COL11A2	ENST00000395194.1	TSL:1	c.607-61C>T		intron	N/A	ENSP00000378620.1
	ENSG00000305994	ENST00000814641.1		n.140G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15367 AN: 151986 Hom.: 1015 Cov.: 31

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.134 AC: 194299 AN: 1455224 Hom.: 13810 AF XY: 0.135 AC XY: 97714 AN XY: 724238

African (AFR) AF: 0.0236 AC: 789 AN: 33434

American (AMR) AF: 0.0611 AC: 2733 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 2370 AN: 26128

East Asian (EAS) AF: 0.112 AC: 4432 AN: 39690

South Asian (SAS) AF: 0.183 AC: 15789 AN: 86214

European-Finnish (FIN) AF: 0.177 AC: 8588 AN: 48428

Middle Eastern (MID) AF: 0.105 AC: 598 AN: 5680

European-Non Finnish (NFE) AF: 0.136 AC: 151537 AN: 1110662

Other (OTH) AF: 0.124 AC: 7463 AN: 60284

GnomAD4 genome AF: 0.101 AC: 15364 AN: 152104 Hom.: 1015 Cov.: 31 AF XY: 0.103 AC XY: 7666 AN XY: 74344

African (AFR) AF: 0.0276 AC: 1145 AN: 41506

American (AMR) AF: 0.0721 AC: 1101 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.108 AC: 561 AN: 5178

South Asian (SAS) AF: 0.182 AC: 877 AN: 4812

European-Finnish (FIN) AF: 0.179 AC: 1894 AN: 10576

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9272 AN: 67966

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.123 Hom.: 4470

Bravo AF: 0.0871

Asia WGS AF: 0.115 AC: 398 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	-0.96
CADD	Benign	0.31
DANN	Benign	0.63
PhyloP100		-0.33
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: rs2855459; hg19: chr6-33154656;