rs12038020

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001852.4(COL9A2):c.1792+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,590,078 control chromosomes in the GnomAD database, including 1,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 294 hom., cov: 32)

Exomes 𝑓: 0.012 ( 733 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.438

Publications

4 publications found

Variant links:

Genes affected

COL9A2 (HGNC:2218): (collagen type IX alpha 2 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. This chain is unusual in that, unlike the other two type IX alpha chains, it contains a covalently attached glycosaminoglycan side chain. Mutations in this gene are associated with multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

COL9A2 Gene-Disease associations (from GenCC):

epiphyseal dysplasia, multiple, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Stickler syndrome, type 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
multiple epiphyseal dysplasia due to collagen 9 anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Stickler syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

COL9A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-40302604-C-T is Benign according to our data. Variant chr1-40302604-C-T is described in ClinVar as [Benign]. Clinvar id is 258377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1792+17G>A		intron_variant	Intron 30 of 31	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 link	c.1792+17G>A	intron_variant	Intron 30 of 31	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.2095+17G>A	intron_variant	Intron 29 of 30	1
COL9A2	ENST00000466267.1 link	n.757+17G>A	intron_variant	Intron 10 of 10	5
COL9A2	ENST00000427563.1 link	n.*17G>A	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6225

AN:

152070

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0304

AC:

6505

AN:

214164

AF XY:

0.0264

show subpopulations

Gnomad AFR exome

AF:

0.0999

Gnomad AMR exome

AF:

0.0652

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0117

AC:

16875

AN:

1437894

Hom.:

733

Cov.:

AF XY:

0.0118

AC XY:

8398

AN XY:

713898

show subpopulations

African (AFR)

AF:

0.109

AC:

3576

AN:

32696

American (AMR)

AF:

0.0617

AC:

2598

AN:

42136

Ashkenazi Jewish (ASJ)

AF:

0.00121

AC:

AN:

25716

East Asian (EAS)

AF:

0.136

AC:

5196

AN:

38090

South Asian (SAS)

AF:

0.0317

AC:

2621

AN:

82594

European-Finnish (FIN)

AF:

0.0120

AC:

594

AN:

49572

Middle Eastern (MID)

AF:

0.00989

AC:

AN:

4248

European-Non Finnish (NFE)

AF:

0.000933

AC:

1029

AN:

1103366

Other (OTH)

AF:

0.0200

AC:

1188

AN:

59476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

907

1814

2720

3627

4534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0410

AC:

6236

AN:

152184

Hom.:

294

Cov.:

AF XY:

0.0410

AC XY:

3053

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.107

AC:

4433

AN:

41516

American (AMR)

AF:

0.0439

AC:

671

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.126

AC:

647

AN:

5152

South Asian (SAS)

AF:

0.0397

AC:

191

AN:

4814

European-Finnish (FIN)

AF:

0.0118

AC:

125

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

68018

Other (OTH)

AF:

0.0355

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.0700

AC:

243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 11, 2016

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.51

(source)

DANN

Benign

0.53

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs12038020

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over