rs2269346

Positions:

• chr6-33191121-C-T

Variant summary

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

The NM_080680.3(COL11A2):​c.82+1038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,214 control chromosomes in the GnomAD database, including 1,216 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 0.093 (1216 hom., cov: 32)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.82+1038G>A		intron_variant		ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.82+1038G>A		intron_variant		5	NM_080680.3	ENSP00000339915	P4
COL11A2	ENST00000395194.1	c.82+1038G>A		intron_variant		1		ENSP00000378620
COL11A2	ENST00000374708.8	c.82+1038G>A		intron_variant		5		ENSP00000363840	A1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14178 AN: 152096 Hom.: 1205 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0933 AC: 14196 AN: 152214 Hom.: 1216 Cov.: 32 AF XY: 0.0951 AC XY: 7075 AN XY: 74410

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0842 Hom.: 1846

Bravo AF: 0.0973

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269346; hg19: chr6-33158898;