rs2855429

Positions:

• chr6-33190412-A-C
• chr6-33190412-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080680.3(COL11A2):​c.83-943T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,100 control chromosomes in the GnomAD database, including 47,153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (47153 hom., cov: 31)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3	c.83-943T>G		intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A2	ENST00000341947.7	c.83-943T>G		intron_variant		5	NM_080680.3	P4
COL11A2	ENST00000395194.1	c.83-943T>G		intron_variant		1
COL11A2	ENST00000374708.8	c.83-943T>G		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118994 AN: 151982 Hom.: 47109 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.783 AC: 119094 AN: 152100 Hom.: 47153 Cov.: 31 AF XY: 0.784 AC XY: 58313 AN XY: 74348

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.801

Alfa AF: 0.741 Hom.: 30552

Bravo AF: 0.793

Asia WGS AF: 0.901 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2855429; hg19: chr6-33158189;