dbSNP rs12038020: COL9A2:c.1792+17G>A (chr1-40302604-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001852.4(COL9A2):c.1792+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,590,078 control chromosomes in the GnomAD database, including 1,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 294 hom., cov: 32)

Exomes 𝑓: 0.012 ( 733 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.438

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-40302604-C-T is Benign according to our data. Variant chr1-40302604-C-T is described in ClinVar as [Benign]. Clinvar id is 258377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40302604-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1792+17G>A		intron_variant	Intron 30 of 31	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 link	c.1792+17G>A	intron_variant	Intron 30 of 31	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 link	n.2095+17G>A	intron_variant	Intron 29 of 30	1
COL9A2	ENST00000466267.1 link	n.757+17G>A	intron_variant	Intron 10 of 10	5
COL9A2	ENST00000427563.1 link	n.*17G>A	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6225

AN:

152070

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0304

AC:

6505

AN:

214164

Hom.:

249

AF XY:

0.0264

AC XY:

3074

AN XY:

116266

show subpopulations

Gnomad AFR exome

AF:

0.0999

Gnomad AMR exome

AF:

0.0652

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.0319

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0117

AC:

16875

AN:

1437894

Hom.:

733

Cov.:

AF XY:

0.0118

AC XY:

8398

AN XY:

713898

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0617

Gnomad4 ASJ exome

AF:

0.00121

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.000933

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0410

AC:

6236

AN:

152184

Hom.:

294

Cov.:

AF XY:

0.0410

AC XY:

3053

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0439

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.0397

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0196

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.0700

AC:

243

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

Dec 11, 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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.51

DANN

Benign

0.53

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