rs143505163

Variant names:

• chr6-33185764-G-A
• rs143505163
• NM_080680.3:c.813C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33185764-G-A
• chr6-33185764-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_080680.3(COL11A2):​c.813C>T​(p.Leu271Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,351,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: COL11A2 NM_080680.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.45
• Publications: 0 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

ENSG00000305994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 6-33185764-G-A is Benign according to our data. Variant chr6-33185764-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 561281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000406 (487/1200642) while in subpopulation NFE AF = 0.000502 (473/941722). AF 95% confidence interval is 0.000464. There are 0 homozygotes in GnomAdExome4. There are 253 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.

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.813C>T	p.Leu271Leu	synonymous	Exon 6 of 66	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.813C>T	p.Leu271Leu	synonymous	Exon 6 of 65	NP_001411037.1
	COL11A2	NM_001424109.1		c.-34C>T		5_prime_UTR	Exon 6 of 66	NP_001411038.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.813C>T	p.Leu271Leu	synonymous	Exon 6 of 66	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.813C>T	p.Leu271Leu	synonymous	Exon 6 of 65	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.799-710C>T		intron	N/A	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 19 AN: 150510 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000237

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 40 AN: 246112 AF XY: 0.000186

Gnomad AFR exome AF: 0.0000664

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000406 AC: 487 AN: 1200642 Hom.: 0 Cov.: 28 AF XY: 0.000425 AC XY: 253 AN XY: 595906

African (AFR) AF: 0.0000771 AC: 2 AN: 25956

American (AMR) AF: 0.00 AC: 0 AN: 37250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16786

East Asian (EAS) AF: 0.00 AC: 0 AN: 16762

South Asian (SAS) AF: 0.00 AC: 0 AN: 82916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4350

European-Non Finnish (NFE) AF: 0.000502 AC: 473 AN: 941722

Other (OTH) AF: 0.000276 AC: 12 AN: 43498

GnomAD4 genome AF: 0.000126 AC: 19 AN: 150510 Hom.: 0 Cov.: 27 AF XY: 0.000109 AC XY: 8 AN XY: 73426

African (AFR) AF: 0.0000735 AC: 3 AN: 40840

American (AMR) AF: 0.00 AC: 0 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000237 AC: 16 AN: 67542

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.000271 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	COL11A2-related disorder (1)
-	-	1	Connective tissue disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		1.5
Mutation Taster		=91/9	polymorphism

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: rs143505163; hg19: chr6-33153541;