rs2076311

Positions:

• chr6-33177592-C-A
• chr6-33177592-C-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.1917+70G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,595,442 control chromosomes in the GnomAD database, including 79,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7753 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71428 hom.)
• Consequence: COL11A2 NM_080680.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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=-0.86).
• BP6: Variant 6-33177592-C-A is Benign according to our data. Variant chr6-33177592-C-A is described in ClinVar as [Benign]. Clinvar id is 674972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3	c.1917+70G>T		intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A2	ENST00000341947.7	c.1917+70G>T		intron_variant		5	NM_080680.3	P4
COL11A2	ENST00000361917.6	c.490+70G>T		intron_variant		5
COL11A2	ENST00000374708.8	c.1659+70G>T		intron_variant		5		A1
COL11A2	ENST00000477772.1	n.136+70G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47900 AN: 151842 Hom.: 7750 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.311 AC: 448969 AN: 1443482 Hom.: 71428 Cov.: 29 AF XY: 0.314 AC XY: 225792 AN XY: 718452

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.315 AC: 47918 AN: 151960 Hom.: 7753 Cov.: 32 AF XY: 0.310 AC XY: 23008 AN XY: 74276

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.323

Alfa AF: 0.317 Hom.: 11220

Bravo AF: 0.318

Asia WGS AF: 0.327 AC: 1140 AN: 3478

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 13, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.58

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: rs2076311; hg19: chr6-33145369;