Variant chr1-40314169-G-T 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.249+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,610,956 control chromosomes in the GnomAD database, including 5,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1239 hom., cov: 32)

Exomes 𝑓: 0.063 ( 4202 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.20

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 1-40314169-G-T is Benign according to our data. Variant chr1-40314169-G-T is described in ClinVar as [Benign]. Clinvar id is 258384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 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.249+36C>A		intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A2	ENST00000372748.8 linkuse as main transcript	c.249+36C>A		intron_variant		1	NM_001852.4	P1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16136

AN:

152020

Hom.:

1227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0800

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0506

Gnomad OTH

AF:

0.0819

GnomAD3 exomes

AF:

0.0879

AC:

22101

AN:

251302

Hom.:

1405

AF XY:

0.0858

AC XY:

11659

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0923

Gnomad ASJ exome

AF:

0.0645

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0427

Gnomad NFE exome

AF:

0.0492

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0625

AC:

91204

AN:

1458818

Hom.:

4202

Cov.:

AF XY:

0.0641

AC XY:

46524

AN XY:

725900

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.0905

Gnomad4 ASJ exome

AF:

0.0640

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0420

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.106

AC:

16172

AN:

152138

Hom.:

1239

Cov.:

AF XY:

0.108

AC XY:

8036

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.0800

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0506

Gnomad4 OTH

AF:

0.0820

Alfa

AF:

0.0632

Hom.:

724

Bravo

AF:

0.112

Asia WGS

AF:

0.171

AC:

596

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	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.83

CADD

Benign

4.7

DANN

Benign

0.49

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