Variant chr1-40304753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001852.4(COL9A2):c.1161+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 1,526,022 control chromosomes in the GnomAD database, including 5,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1267 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3763 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.856

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=-0.85).

BP6

Variant 1-40304753-G-A is Benign according to our data. Variant chr1-40304753-G-A is described in ClinVar as [Benign]. Clinvar id is 258368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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.1161+41C>T		intron_variant		ENST00000372748.8	NP_001843.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
COL9A2	ENST00000372748.8 linkuse as main transcript	c.1161+41C>T	intron_variant	1	NM_001852.4	ENSP00000361834	P1
COL9A2	ENST00000482722.5 linkuse as main transcript	n.1464+41C>T	intron_variant, non_coding_transcript_variant	1
COL9A2	ENST00000466267.1 linkuse as main transcript	n.126+41C>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16284

AN:

152132

Hom.:

1254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0495

Gnomad OTH

AF:

0.0783

GnomAD3 exomes

AF:

0.0920

AC:

14081

AN:

153012

Hom.:

920

AF XY:

0.0895

AC XY:

7205

AN XY:

80490

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0577

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0523

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0689

GnomAD4 exome

AF:

0.0608

AC:

83502

AN:

1373772

Hom.:

3763

Cov.:

AF XY:

0.0618

AC XY:

41921

AN XY:

678156

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.0587

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.0506

Gnomad4 NFE exome

AF:

0.0459

Gnomad4 OTH exome

AF:

0.0718

GnomAD4 genome

AF:

0.107

AC:

16335

AN:

152250

Hom.:

1267

Cov.:

AF XY:

0.109

AC XY:

8130

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.0868

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0503

Gnomad4 NFE

AF:

0.0495

Gnomad4 OTH

AF:

0.0818

Alfa

AF:

0.0447

Hom.:

Bravo

AF:

0.114

Asia WGS

AF:

0.181

AC:

630

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.6

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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