rs3737815

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001852.4(COL9A2):c.630+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,654 control chromosomes in the GnomAD database, including 24,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1917 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23065 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0370

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-40311080-C-A is Benign according to our data. Variant chr1-40311080-C-A is described in ClinVar as [Benign]. Clinvar id is 258392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40311080-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A2	NM_001852.4 linkuse as main transcript	c.630+13G>T		intron_variant		ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
COL9A2	ENST00000372748.8 linkuse as main transcript	c.630+13G>T	intron_variant	1	NM_001852.4	ENSP00000361834	P1
COL9A2	ENST00000482722.5 linkuse as main transcript	n.933+13G>T	intron_variant, non_coding_transcript_variant	1
COL9A2	ENST00000417105.6 linkuse as main transcript	c.348+13G>T	intron_variant	5		ENSP00000388493
COL9A2	ENST00000488463.6 linkuse as main transcript	n.681+13G>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21272

AN:

152082

Hom.:

1915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0532

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.0977

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.174

AC:

43816

AN:

251264

Hom.:

4721

AF XY:

0.168

AC XY:

22848

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.0976

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.168

AC:

245050

AN:

1461454

Hom.:

23065

Cov.:

AF XY:

0.166

AC XY:

120408

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.0987

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.162

GnomAD4 genome

AF:

0.140

AC:

21274

AN:

152200

Hom.:

1917

Cov.:

AF XY:

0.141

AC XY:

10462

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0532

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.0971

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.115

Hom.:

322

Bravo

AF:

0.141

Asia WGS

AF:

0.228

AC:

793

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epiphyseal dysplasia, multiple, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.7

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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