Genetic Variant COL11A2:c.2214+88G>C (chr6-33176171-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_080680.3(COL11A2):c.2214+88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,602,926 control chromosomes in the GnomAD database, including 155,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 17233 hom., cov: 31)

Exomes 𝑓: 0.43 ( 138284 hom. )

Consequence

COL11A2
NM_080680.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.470

Variant links:

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]

COL11A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 6-33176171-C-G is Benign according to our data. Variant chr6-33176171-C-G is described in ClinVar as [Benign]. Clinvar id is 674768.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3 link	c.2214+88G>C		intron_variant	Intron 28 of 65	ENST00000341947.7	NP_542411.2	P13942A0A0C4DFS1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL11A2	ENST00000341947.7 link	c.2214+88G>C	intron_variant	Intron 28 of 65	5	NM_080680.3	ENSP00000339915.2	A0A0C4DFS1
COL11A2	ENST00000374708.8 link	c.1956+88G>C	intron_variant	Intron 26 of 63	5		ENSP00000363840.4	Q4VXY6
COL11A2	ENST00000361917.6 link	c.786+88G>C	intron_variant	Intron 15 of 23	5		ENSP00000355123.2	H0YIS1
COL11A2	ENST00000477772.1 link	n.272+838G>C	intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71106

AN:

151726

Hom.:

17204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.429

AC:

623104

AN:

1451082

Hom.:

138284

Cov.:

AF XY:

0.431

AC XY:

311285

AN XY:

722512

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.595

Gnomad4 ASJ exome

AF:

0.437

Gnomad4 EAS exome

AF:

0.752

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.469

AC:

71188

AN:

151844

Hom.:

17233

Cov.:

AF XY:

0.475

AC XY:

35287

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.520

Gnomad4 ASJ

AF:

0.423

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.274

Hom.:

640

Bravo

AF:

0.477

Asia WGS

AF:

0.573

AC:

1990

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.95

CADD

Benign

1.2

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over