rs986521

chr6-33168368-G-Achr6-33168368-G-Cchr6-33168368-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080680.3(COL11A2):c.3960+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 861,220 control chromosomes in the GnomAD database, including 272,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (50770 hom., cov: 28)
  • Exomes 𝑓: 0.78 (221899 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-33168368-G-A is Benign according to our data. Variant chr6-33168368-G-A is described in ClinVar as [Benign]. Clinvar id is 1271419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3	c.3960+151C>T		intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A2	ENST00000341947.7	c.3960+151C>T		intron_variant		5	NM_080680.3	P4
COL11A2	ENST00000374708.8	c.3702+151C>T		intron_variant		5		A1
COL11A2	ENST00000477772.1	n.273-2552C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 122605 AN: 150106 Hom.: 50716 Cov.: 28

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.913

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.784 AC: 557761 AN: 710996 Hom.: 221899 AF XY: 0.790 AC XY: 296733 AN XY: 375778

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.902

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.743

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.817 AC: 122716 AN: 150224 Hom.: 50770 Cov.: 28 AF XY: 0.818 AC XY: 60059 AN XY: 73438

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.850

Alfa AF: 0.781 Hom.: 47034

Bravo AF: 0.838

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.59
Dann	Benign	0.40

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: rs986521; hg19: chr6-33136145;