Variant 1-40303502-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.1548+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,612,116 control chromosomes in the GnomAD database, including 1,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 750 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1209 hom. )

Consequence

COL9A2
NM_001852.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.41

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:

COL9A2 (HGNC:):

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=-0.95).

BP6

Variant 1-40303502-G-T is Benign according to our data. Variant chr1-40303502-G-T is described in ClinVar as [Benign]. Clinvar id is 258376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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.1548+28C>A		intron_variant		ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL9A2	ENST00000372748.8 linkuse as main transcript	c.1548+28C>A	intron_variant	1	NM_001852.4	ENSP00000361834.3	Q14055
COL9A2	ENST00000482722.5 linkuse as main transcript	n.1851+28C>A	intron_variant	1
COL9A2	ENST00000427563.1 linkuse as main transcript	n.359+28C>A	intron_variant	3
COL9A2	ENST00000466267.1 linkuse as main transcript	n.513+28C>A	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0700

AC:

10639

AN:

152074

Hom.:

743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0447

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0387

AC:

9468

AN:

244612

Hom.:

406

AF XY:

0.0350

AC XY:

4673

AN XY:

133488

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.0605

Gnomad ASJ exome

AF:

0.0403

Gnomad EAS exome

AF:

0.0218

Gnomad SAS exome

AF:

0.0357

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0262

AC:

38226

AN:

1459924

Hom.:

1209

Cov.:

AF XY:

0.0261

AC XY:

18967

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.0580

Gnomad4 ASJ exome

AF:

0.0409

Gnomad4 EAS exome

AF:

0.0327

Gnomad4 SAS exome

AF:

0.0352

Gnomad4 FIN exome

AF:

0.0249

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0337

GnomAD4 genome

AF:

0.0702

AC:

10678

AN:

152192

Hom.:

750

Cov.:

AF XY:

0.0701

AC XY:

5219

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0446

Gnomad4 ASJ

AF:

0.0406

Gnomad4 EAS

AF:

0.0257

Gnomad4 SAS

AF:

0.0336

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0496

Alfa

AF:

0.0496

Hom.:

Bravo

AF:

0.0767

Asia WGS

AF:

0.0670

AC:

232

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 16, 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

-0.95

CADD

Benign

0.24

DANN

Benign

0.66

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