Variant chr1-40300870-A-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.*312T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 320,982 control chromosomes in the GnomAD database, including 799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 615 hom., cov: 32)

Exomes 𝑓: 0.031 ( 184 hom. )

Consequence

COL9A2
NM_001852.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.29

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:

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=-0.92).

BP6

Variant 1-40300870-A-T is Benign according to our data. Variant chr1-40300870-A-T is described in ClinVar as [Benign]. Clinvar id is 297285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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.*312T>A		3_prime_UTR_variant	32/32	ENST00000372748.8	NP_001843.1	Q14055

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A2	ENST00000372748 linkuse as main transcript	c.*312T>A		3_prime_UTR_variant	32/32	1	NM_001852.4	ENSP00000361834.3		Q14055
COL9A2	ENST00000482722.5 linkuse as main transcript	n.2685T>A		non_coding_transcript_exon_variant	31/31	1

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9864

AN:

152054

Hom.:

608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0258

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0430

GnomAD4 exome

AF:

0.0308

AC:

5194

AN:

168810

Hom.:

184

Cov.:

AF XY:

0.0305

AC XY:

2697

AN XY:

88356

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0508

Gnomad4 ASJ exome

AF:

0.0359

Gnomad4 EAS exome

AF:

0.0328

Gnomad4 SAS exome

AF:

0.0324

Gnomad4 FIN exome

AF:

0.0254

Gnomad4 NFE exome

AF:

0.0213

Gnomad4 OTH exome

AF:

0.0345

GnomAD4 genome

AF:

0.0651

AC:

9903

AN:

152172

Hom.:

615

Cov.:

AF XY:

0.0653

AC XY:

4859

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.0423

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.0259

Gnomad4 SAS

AF:

0.0344

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0458

Alfa

AF:

0.0541

Hom.:

Bravo

AF:

0.0706

Asia WGS

AF:

0.0670

AC:

231

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epiphyseal dysplasia, multiple, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

DANN

Benign

0.46

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