6-33192648-G-T

Variant names:

• chr6-33192648-G-T
• rs9277935
• XM_017010250.2:c.-132C>A

Variant summary

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

The NM_001424111.1(COL11A2):​c.-765+377C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 298,010 control chromosomes in the GnomAD database, including 9,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5139 hom., cov: 30)
  • Exomes 𝑓: 0.22 (4346 hom.)
• Consequence: COL11A2 NM_001424111.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.170

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=-0.84).
• BP6: Variant 6-33192648-G-T is Benign according to our data. Variant chr6-33192648-G-T is described in ClinVar as [Benign]. Clinvar id is 669616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.-408C>A		upstream_gene_variant		ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.-408C>A		upstream_gene_variant		5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000395194.1	c.-408C>A		upstream_gene_variant		1		ENSP00000378620.1
COL11A2	ENST00000374708.8	c.-408C>A		upstream_gene_variant		5		ENSP00000363840.4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36837 AN: 151764 Hom.: 5114 Cov.: 30

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.217 AC: 31659 AN: 146128 Hom.: 4346 AF XY: 0.219 AC XY: 17117 AN XY: 78196

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.243 AC: 36910 AN: 151882 Hom.: 5139 Cov.: 30 AF XY: 0.246 AC XY: 18257 AN XY: 74232

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.250

Alfa AF: 0.219 Hom.: 4486

Bravo AF: 0.241

Asia WGS AF: 0.374 AC: 1297 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.84
CADD	Benign	3.0
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9277935; hg19: chr6-33160425;