1-40303513-C-G

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.1548+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,612,730 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 22 hom., cov: 32)

Exomes 𝑓: 0.018 ( 511 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.236

Publications

3 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=-0.78).

BP6

Variant 1-40303513-C-G is Benign according to our data. Variant chr1-40303513-C-G is described in ClinVar as Benign. ClinVar VariationId is 258375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1548+17G>C		intron_variant	Intron 28 of 31	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL9A2	ENST00000372748.8 link	c.1548+17G>C	intron_variant	Intron 28 of 31	1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5 link	n.1851+17G>C	intron_variant	Intron 27 of 30	1
COL9A2	ENST00000427563.1 link	n.359+17G>C	intron_variant	Intron 6 of 6	3
COL9A2	ENST00000466267.1 link	n.513+17G>C	intron_variant	Intron 8 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2500

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.0236

AC:

5795

AN:

245336

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0373

Gnomad FIN exome

AF:

0.00358

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0184

AC:

26821

AN:

1460480

Hom.:

511

Cov.:

AF XY:

0.0202

AC XY:

14653

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.0179

AC:

599

AN:

33466

American (AMR)

AF:

0.0210

AC:

939

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

662

AN:

26120

East Asian (EAS)

AF:

0.0495

AC:

1964

AN:

39690

South Asian (SAS)

AF:

0.0756

AC:

6516

AN:

86196

European-Finnish (FIN)

AF:

0.00451

AC:

236

AN:

52378

Middle Eastern (MID)

AF:

0.0293

AC:

169

AN:

5766

European-Non Finnish (NFE)

AF:

0.0131

AC:

14520

AN:

1111828

Other (OTH)

AF:

0.0201

AC:

1216

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1557

3114

4670

6227

7784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.0164

AC:

2498

AN:

152250

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1311

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0161

AC:

670

AN:

41544

American (AMR)

AF:

0.0195

AC:

298

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3466

East Asian (EAS)

AF:

0.0419

AC:

217

AN:

5174

South Asian (SAS)

AF:

0.0793

AC:

382

AN:

4820

European-Finnish (FIN)

AF:

0.00282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

759

AN:

67996

Other (OTH)

AF:

0.0203

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

121

243

364

486

607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00783

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.0550

AC:

191

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 06, 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

-0.78

CADD

Benign

3.4

(source)

DANN

Benign

0.71

PhyloP100

-0.24

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)

0.010

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