rs72944910

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1161+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,526,022 control chromosomes in the GnomAD database, including 5,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1267 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3763 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.856

Publications

2 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=-0.85).

BP6

Variant 1-40304753-G-A is Benign according to our data. Variant chr1-40304753-G-A is described in ClinVar as [Benign]. Clinvar id is 258368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1161+41C>T		intron_variant	Intron 22 of 31	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 link	c.1161+41C>T	intron_variant	Intron 22 of 31	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.1464+41C>T	intron_variant	Intron 21 of 30	1
COL9A2	ENST00000466267.1 link	n.126+41C>T	intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16284

AN:

152132

Hom.:

1254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0495

Gnomad OTH

AF:

0.0783

GnomAD2 exomes

AF:

0.0920

AC:

14081

AN:

153012

AF XY:

0.0895

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0577

Gnomad EAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0689

GnomAD4 exome

AF:

0.0608

AC:

83502

AN:

1373772

Hom.:

3763

Cov.:

AF XY:

0.0618

AC XY:

41921

AN XY:

678156

show subpopulations

African (AFR)

AF:

0.232

AC:

7204

AN:

31106

American (AMR)

AF:

0.111

AC:

3931

AN:

35418

Ashkenazi Jewish (ASJ)

AF:

0.0587

AC:

1453

AN:

24762

East Asian (EAS)

AF:

0.179

AC:

6355

AN:

35574

South Asian (SAS)

AF:

0.116

AC:

9102

AN:

78466

European-Finnish (FIN)

AF:

0.0506

AC:

2422

AN:

47866

Middle Eastern (MID)

AF:

0.0622

AC:

326

AN:

5240

European-Non Finnish (NFE)

AF:

0.0459

AC:

48615

AN:

1058294

Other (OTH)

AF:

0.0718

AC:

4094

AN:

57046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

4050

8100

12151

16201

20251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2022

4044

6066

8088

10110

<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:

0.107

AC:

16335

AN:

152250

Hom.:

1267

Cov.:

AF XY:

0.109

AC XY:

8130

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.218

AC:

9067

AN:

41546

American (AMR)

AF:

0.0868

AC:

1327

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

206

AN:

3470

East Asian (EAS)

AF:

0.183

AC:

941

AN:

5156

South Asian (SAS)

AF:

0.133

AC:

640

AN:

4824

European-Finnish (FIN)

AF:

0.0503

AC:

534

AN:

10618

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0495

AC:

3367

AN:

68022

Other (OTH)

AF:

0.0818

AC:

173

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

737

1475

2212

2950

3687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0447

Hom.:

Bravo

AF:

0.114

Asia WGS

AF:

0.181

AC:

630

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.85

CADD

Benign

6.6

(source)

DANN

Benign

0.44

PhyloP100

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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