1-40312128-T-G

Variant names:

Variant summary

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

The ENST00000482722.5(COL9A2):n.651A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,593,676 control chromosomes in the GnomAD database, including 58,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7637 hom., cov: 31)

Exomes 𝑓: 0.25 ( 51322 hom. )

Consequence

COL9A2
ENST00000482722.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.550

Publications

14 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=-0.83).

BP6

Variant 1-40312128-T-G is Benign according to our data. Variant chr1-40312128-T-G is described in ClinVar as Benign. ClinVar VariationId is 258387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.364-16A>C		intron_variant	Intron 7 of 31	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8 link	c.364-16A>C		intron_variant	Intron 7 of 31	1	NM_001852.4	ENSP00000361834.3		Q14055

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44827

AN:

151352

Hom.:

7617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.160

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.247

GnomAD2 exomes

AF:

0.300

AC:

66243

AN:

220972

AF XY:

0.288

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.249

AC:

358888

AN:

1442212

Hom.:

51322

Cov.:

AF XY:

0.248

AC XY:

177478

AN XY:

715728

show subpopulations

African (AFR)

AF:

0.397

AC:

13189

AN:

33230

American (AMR)

AF:

0.425

AC:

17154

AN:

40352

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5287

AN:

25614

East Asian (EAS)

AF:

0.722

AC:

28189

AN:

39058

South Asian (SAS)

AF:

0.260

AC:

21516

AN:

82626

European-Finnish (FIN)

AF:

0.253

AC:

13281

AN:

52452

Middle Eastern (MID)

AF:

0.180

AC:

1029

AN:

5704

European-Non Finnish (NFE)

AF:

0.221

AC:

243498

AN:

1103426

Other (OTH)

AF:

0.264

AC:

15745

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

11897

23793

35690

47586

59483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8764

17528

26292

35056

43820

<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:

0.296

AC:

44891

AN:

151464

Hom.:

7637

Cov.:

AF XY:

0.300

AC XY:

22159

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.384

AC:

15800

AN:

41196

American (AMR)

AF:

0.351

AC:

5350

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

720

AN:

3470

East Asian (EAS)

AF:

0.705

AC:

3617

AN:

5132

South Asian (SAS)

AF:

0.288

AC:

1378

AN:

4782

European-Finnish (FIN)

AF:

0.244

AC:

2554

AN:

10486

Middle Eastern (MID)

AF:

0.172

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.216

AC:

14665

AN:

67858

Other (OTH)

AF:

0.245

AC:

515

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1511

3022

4534

6045

7556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.162

Hom.:

410

Bravo

AF:

0.312

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

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

- -

Sep 29, 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

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

-0.83

CADD

Benign

0.99

(source)

DANN

Benign

0.51

PhyloP100

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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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