rs530508572

Positions:

chr6-33178989-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_080680.3(COL11A2):c.1612-16T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

COL11A2
NM_080680.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0190

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-33178989-A-T is Benign according to our data. Variant chr6-33178989-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 561278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000855 (125/1461862) while in subpopulation SAS AF= 0.000719 (62/86258). AF 95% confidence interval is 0.000575. There are 1 homozygotes in gnomad4_exome. There are 66 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A2	NM_080680.3 linkuse as main transcript	c.1612-16T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000341947.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL11A2	ENST00000341947.7 linkuse as main transcript	c.1612-16T>A	splice_polypyrimidine_tract_variant, intron_variant	5	NM_080680.3	P4
COL11A2	ENST00000361917.6 linkuse as main transcript	c.239-16T>A	splice_polypyrimidine_tract_variant, intron_variant	5
COL11A2	ENST00000374708.8 linkuse as main transcript	c.1354-16T>A	splice_polypyrimidine_tract_variant, intron_variant	5		A1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000203

AC:

AN:

250866

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000855

AC:

125

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Jun 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.7

DANN

Benign

0.82

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