Variant 1-40302811-TGGAGGGAGGGAG-TGGAGGGAGGGAGGGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001852.4(COL9A2):c.1604-6_1604-3dupCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 554,618 control chromosomes in the GnomAD database, including 185 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 53 hom., cov: 31)

Exomes 𝑓: 0.034 ( 132 hom. )

Consequence

COL9A2
NM_001852.4 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.54

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-40302811-T-TGGAG is Benign according to our data. Variant chr1-40302811-T-TGGAG is described in ClinVar as [Benign]. Clinvar id is 1167800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1604-6_1604-3dupCTCC		splice_region_variant, intron_variant		ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 link	c.1604-3_1604-2insCTCC	splice_region_variant, intron_variant	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.1907-3_1907-2insCTCC	splice_region_variant, intron_variant	1
COL9A2	ENST00000427563.1 link	n.360-3_360-2insCTCC	splice_region_variant, intron_variant	3
COL9A2	ENST00000466267.1 link	n.569-3_569-2insCTCC	splice_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

3614

AN:

125770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.0174

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.0298

AC:

4095

AN:

137322

Hom.:

AF XY:

0.0294

AC XY:

2185

AN XY:

74414

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.0528

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.0241

Gnomad SAS exome

AF:

0.0366

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0335

AC:

14374

AN:

428750

Hom.:

132

Cov.:

AF XY:

0.0343

AC XY:

7932

AN XY:

231318

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.0534

Gnomad4 ASJ exome

AF:

0.0596

Gnomad4 EAS exome

AF:

0.0794

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0287

AC:

3617

AN:

125868

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

1744

AN XY:

59798

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0413

Gnomad4 EAS

AF:

0.0279

Gnomad4 SAS

AF:

0.0386

Gnomad4 FIN

AF:

0.0302

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0233

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 25, 2016	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Epiphyseal dysplasia, multiple, 2;C3280342:Stickler syndrome, type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 14, 2021

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over