1-40305760-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001852.4(COL9A2):c.1062G>A(p.Pro354Pro) 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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
COL9A2	NM_001852.4 link	c.1062G>A	p.Pro354Pro	synonymous_variant	Exon 21 of 32	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748.8 link	c.1062G>A	p.Pro354Pro	synonymous_variant	Exon 21 of 32	1	NM_001852.4	ENSP00000361834.3		Q14055
COL9A2	ENST00000482722.5 link	n.1365G>A		non_coding_transcript_exon_variant	Exon 20 of 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

GnomAD2 exomes

AF:

0.0305

AC:

7657

AN:

250880

AF XY:

0.0267

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 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

African (AFR)

AF:

0.109

AC:

3656

AN:

33462

American (AMR)

AF:

0.0653

AC:

2920

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00126

AC:

AN:

26136

East Asian (EAS)

AF:

0.109

AC:

4340

AN:

39692

South Asian (SAS)

AF:

0.0311

AC:

2686

AN:

86256

European-Finnish (FIN)

AF:

0.0124

AC:

659

AN:

53360

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000968

AC:

1076

AN:

1111940

Other (OTH)

AF:

0.0181

AC:

1094

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

906

1811

2717

3622

4528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0393

AC:

5991

AN:

152260

Hom.:

275

Cov.:

AF XY:

0.0392

AC XY:

2917

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.104

AC:

4336

AN:

41536

American (AMR)

AF:

0.0439

AC:

672

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.0988

AC:

511

AN:

5172

South Asian (SAS)

AF:

0.0363

AC:

175

AN:

4824

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

68028

Other (OTH)

AF:

0.0340

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

281

562

844

1125

1406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0160

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

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 13, 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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 24, 2018

Athena Diagnostics

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.7

(source)

DANN

Benign

0.62

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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 for variant 1:40305760 C>T . It may be empty.

1-40305760-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over