rs6674856

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.1793-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 1,610,114 control chromosomes in the GnomAD database, including 1,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 734 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1203 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.529

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=-0.88).

BP6

Variant 1-40301906-A-G is Benign according to our data. Variant chr1-40301906-A-G is described in ClinVar as Benign. ClinVar VariationId is 258378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1793-17T>C		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.1793-17T>C	intron_variant	Intron 30 of 31	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.2096-17T>C	intron_variant	Intron 29 of 30	1
COL9A2	ENST00000466267.1 link	n.758-17T>C	intron_variant	Intron 10 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10579

AN:

152132

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0442

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0454

GnomAD2 exomes

AF:

0.0405

AC:

9919

AN:

244810

AF XY:

0.0364

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.0410

Gnomad EAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.0243

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0263

AC:

38390

AN:

1457864

Hom.:

1203

Cov.:

AF XY:

0.0262

AC XY:

19024

AN XY:

725182

show subpopulations

African (AFR)

AF:

0.198

AC:

6610

AN:

33318

American (AMR)

AF:

0.0589

AC:

2617

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

1066

AN:

26048

East Asian (EAS)

AF:

0.0330

AC:

1310

AN:

39642

South Asian (SAS)

AF:

0.0355

AC:

3040

AN:

85646

European-Finnish (FIN)

AF:

0.0250

AC:

1333

AN:

53280

Middle Eastern (MID)

AF:

0.0252

AC:

145

AN:

5764

European-Non Finnish (NFE)

AF:

0.0182

AC:

20241

AN:

1109510

Other (OTH)

AF:

0.0337

AC:

2028

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1747

3494

5240

6987

8734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0697

AC:

10618

AN:

152250

Hom.:

734

Cov.:

AF XY:

0.0696

AC XY:

5185

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.185

AC:

7684

AN:

41518

American (AMR)

AF:

0.0441

AC:

675

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3472

East Asian (EAS)

AF:

0.0262

AC:

136

AN:

5182

South Asian (SAS)

AF:

0.0340

AC:

164

AN:

4824

European-Finnish (FIN)

AF:

0.0230

AC:

244

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0215

AC:

1463

AN:

68012

Other (OTH)

AF:

0.0482

AC:

102

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

487

974

1462

1949

2436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0519

Hom.:

Bravo

AF:

0.0760

Asia WGS

AF:

0.0660

AC:

228

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 10, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

(source)

DANN

Benign

0.57

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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