rs6676013

Positions:

chr1-40305760-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001852.4(COL9A2):c.1062G>A(p.Pro354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,974 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 275 hom., cov: 32)

Exomes 𝑓: 0.011 ( 624 hom. )

Consequence

COL9A2
NM_001852.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.52

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-40305760-C-T is Benign according to our data. Variant chr1-40305760-C-T is described in ClinVar as [Benign]. Clinvar id is 258365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40305760-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.1062G>A	p.Pro354=	synonymous_variant	21/32	ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8 linkuse as main transcript	c.1062G>A	p.Pro354=	synonymous_variant	21/32	1	NM_001852.4	ENSP00000361834	P1
COL9A2	ENST00000482722.5 linkuse as main transcript	n.1365G>A		non_coding_transcript_exon_variant	20/31	1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5981

AN:

152142

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0990

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0305

AC:

7657

AN:

250880

Hom.:

306

AF XY:

0.0267

AC XY:

3620

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0700

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0113

AC:

16525

AN:

1461714

Hom.:

624

Cov.:

AF XY:

0.0113

AC XY:

8232

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0653

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0124

Gnomad4 NFE exome

AF:

0.000968

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0393

AC:

5991

AN:

152260

Hom.:

275

Cov.:

AF XY:

0.0392

AC XY:

2917

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0439

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0988

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.0340

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0458

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 13, 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. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
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 13, 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

-0.49

CADD

Benign

2.7

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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