1-40312128-T-G

Variant summary

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

The NM_001852.4(COL9A2):c.364-16A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,593,676 control chromosomes in the GnomAD database, including 58,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7637 hom., cov: 31)

Exomes 𝑓: 0.25 ( 51322 hom. )

Consequence

COL9A2
NM_001852.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.550

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=-0.83).

BP6

Variant 1-40312128-T-G is Benign according to our data. Variant chr1-40312128-T-G is described in ClinVar as [Benign]. Clinvar id is 258387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40312128-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A2	NM_001852.4 linkuse as main transcript	c.364-16A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A2	ENST00000372748.8 linkuse as main transcript	c.364-16A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001852.4	P1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44827

AN:

151352

Hom.:

7617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.160

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.300

AC:

66243

AN:

220972

Hom.:

12155

AF XY:

0.288

AC XY:

34133

AN XY:

118632

show subpopulations

Gnomad AFR exome

AF:

0.382

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.249

AC:

358888

AN:

1442212

Hom.:

51322

Cov.:

AF XY:

0.248

AC XY:

177478

AN XY:

715728

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.296

AC:

44891

AN:

151464

Hom.:

7637

Cov.:

AF XY:

0.300

AC XY:

22159

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.162

Hom.:

410

Bravo

AF:

0.312

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

0.99

Dann

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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