1-40302811-TGGAGGGAGGGAG-TGGAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001852.4(COL9A2):c.1604-10_1604-3delCTCCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 551,572 control chromosomes in the GnomAD database, including 1,273 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 512 hom., cov: 30)

Exomes 𝑓: 0.017 ( 761 hom. )

Consequence

COL9A2
NM_001852.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.54

Publications

1 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 -16 ACMG points.

BP6

Variant 1-40302811-TGGAGGGAG-T is Benign according to our data. Variant chr1-40302811-TGGAGGGAG-T is described in ClinVar as Benign. ClinVar VariationId is 196621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1604-10_1604-3delCTCCCTCC		splice_region_variant, intron_variant	Intron 29 of 31	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL9A2	ENST00000372748.8 link	c.1604-10_1604-3delCTCCCTCC	splice_region_variant, intron_variant	Intron 29 of 31	1	NM_001852.4	ENSP00000361834.3
COL9A2	ENST00000482722.5 link	n.1907-10_1907-3delCTCCCTCC	splice_region_variant, intron_variant	Intron 28 of 30	1
COL9A2	ENST00000427563.1 link	n.360-10_360-3delCTCCCTCC	splice_region_variant, intron_variant	Intron 6 of 6	3
COL9A2	ENST00000466267.1 link	n.569-10_569-3delCTCCCTCC	splice_region_variant, intron_variant	Intron 9 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

6743

AN:

125844

Hom.:

507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00800

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000569

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.0139

Gnomad NFE

AF:

0.000688

Gnomad OTH

AF:

0.0286

GnomAD2 exomes

AF:

0.0106

AC:

1461

AN:

137322

AF XY:

0.00844

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.00855

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00606

GnomAD4 exome

AF:

0.0174

AC:

7397

AN:

425630

Hom.:

761

AF XY:

0.0139

AC XY:

3192

AN XY:

229902

show subpopulations

African (AFR)

AF:

0.316

AC:

5475

AN:

17328

American (AMR)

AF:

0.0116

AC:

330

AN:

28398

Ashkenazi Jewish (ASJ)

AF:

0.000240

AC:

AN:

12510

East Asian (EAS)

AF:

0.000548

AC:

AN:

12776

South Asian (SAS)

AF:

0.00125

AC:

AN:

60842

European-Finnish (FIN)

AF:

0.000146

AC:

AN:

27372

Middle Eastern (MID)

AF:

0.0192

AC:

AN:

2446

European-Non Finnish (NFE)

AF:

0.00292

AC:

715

AN:

244578

Other (OTH)

AF:

0.0382

AC:

740

AN:

19380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.658

Heterozygous variant carriers

197

394

590

787

984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<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:

0.0538

AC:

6778

AN:

125942

Hom.:

512

Cov.:

AF XY:

0.0546

AC XY:

3270

AN XY:

59836

show subpopulations

African (AFR)

AF:

0.183

AC:

6425

AN:

35162

American (AMR)

AF:

0.0192

AC:

238

AN:

12388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3148

East Asian (EAS)

AF:

0.000569

AC:

AN:

3514

South Asian (SAS)

AF:

0.00117

AC:

AN:

3424

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

5964

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.000688

AC:

AN:

59562

Other (OTH)

AF:

0.0323

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

261

522

782

1043

1304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.00164

Hom.:

Bravo

AF:

0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 15, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Feb 04, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

PhyloP100

2.5

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

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