rs56326652

Variant names:

Variant summary

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

The NM_001852.4(COL9A2):c.738+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,613,950 control chromosomes in the GnomAD database, including 2,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 217 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2364 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.267

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=-0.84).

BP6

Variant 1-40310254-A-G is Benign according to our data. Variant chr1-40310254-A-G is described in ClinVar as [Benign]. Clinvar id is 258394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40310254-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.738+10T>C		intron_variant	Intron 14 of 31	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 link	c.738+10T>C	intron_variant	Intron 14 of 31	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.1041+10T>C	intron_variant	Intron 13 of 30	1
COL9A2	ENST00000488463.6 link	n.789+10T>C	intron_variant	Intron 13 of 13	5
COL9A2	ENST00000417105.6 link	c.*36T>C	downstream_gene_variant		5		ENSP00000388493.2	H0Y409

Frequencies

GnomAD3 genomes

AF:

0.0426

AC:

6481

AN:

152114

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.0392

GnomAD3 exomes

AF:

0.0444

AC:

11170

AN:

251408

Hom.:

333

AF XY:

0.0458

AC XY:

6221

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0442

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.0710

Gnomad NFE exome

AF:

0.0625

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0544

AC:

79587

AN:

1461718

Hom.:

2364

Cov.:

AF XY:

0.0542

AC XY:

39403

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00848

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.0468

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0298

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0611

Gnomad4 OTH exome

AF:

0.0474

GnomAD4 genome

AF:

0.0426

AC:

6480

AN:

152232

Hom.:

217

Cov.:

AF XY:

0.0429

AC XY:

3191

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.0290

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0303

Gnomad4 FIN

AF:

0.0772

Gnomad4 NFE

AF:

0.0647

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0486

Hom.:

Bravo

AF:

0.0365

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 17, 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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epiphyseal dysplasia, multiple, 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Connective tissue disorder

Benign:1

May 12, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.84

CADD

Benign

5.4

DANN

Benign

0.64

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

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