Variant 1-40303513-C-G 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.1548+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,612,730 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 22 hom., cov: 32)

Exomes 𝑓: 0.018 ( 511 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.236

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-40303513-C-G is Benign according to our data. Variant chr1-40303513-C-G is described in ClinVar as [Benign]. Clinvar id is 258375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-40303513-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0727 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.1548+17G>C		intron_variant		ENST00000372748.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
COL9A2	ENST00000372748.8 linkuse as main transcript	c.1548+17G>C	intron_variant	1	NM_001852.4	P1
COL9A2	ENST00000482722.5 linkuse as main transcript	n.1851+17G>C	intron_variant, non_coding_transcript_variant	1
COL9A2	ENST00000427563.1 linkuse as main transcript	n.359+17G>C	intron_variant, non_coding_transcript_variant	3
COL9A2	ENST00000466267.1 linkuse as main transcript	n.513+17G>C	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2500

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0236

AC:

5795

AN:

245336

Hom.:

129

AF XY:

0.0261

AC XY:

3494

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0373

Gnomad SAS exome

AF:

0.0767

Gnomad FIN exome

AF:

0.00358

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0184

AC:

26821

AN:

1460480

Hom.:

511

Cov.:

AF XY:

0.0202

AC XY:

14653

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0495

Gnomad4 SAS exome

AF:

0.0756

Gnomad4 FIN exome

AF:

0.00451

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

AF:

0.0164

AC:

2498

AN:

152250

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1311

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.0419

Gnomad4 SAS

AF:

0.0793

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00783

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 06, 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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.4

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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