Variant chr12-47995240-C-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_001844.5(COL2A1):c.762+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,606,170 control chromosomes in the GnomAD database, including 95,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6384 hom., cov: 32)

Exomes 𝑓: 0.34 ( 89160 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.133

Variant links:

Genes affected

COL2A1 (HGNC:2200): (collagen type II alpha 1 chain) This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]

COL2A1 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=-0.82).

BP6

Variant 12-47995240-C-T is Benign according to our data. Variant chr12-47995240-C-T is described in ClinVar as [Benign]. Clinvar id is 258244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47995240-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5 linkuse as main transcript	c.762+15G>A		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.762+15G>A		intron_variant		1	NM_001844.5	P1	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.555+15G>A		intron_variant		1			P02458-1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39032

AN:

152092

Hom.:

6382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.291

AC:

73255

AN:

251384

Hom.:

12505

AF XY:

0.300

AC XY:

40781

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0608

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.00832

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.376

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.340

AC:

494035

AN:

1453958

Hom.:

89160

Cov.:

AF XY:

0.340

AC XY:

246005

AN XY:

723830

show subpopulations

Gnomad4 AFR exome

AF:

0.0555

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.365

Gnomad4 EAS exome

AF:

0.00474

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.256

AC:

39039

AN:

152212

Hom.:

6384

Cov.:

AF XY:

0.254

AC XY:

18873

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0679

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.308

Hom.:

1848

Bravo

AF:

0.241

Asia WGS

AF:

0.163

AC:

570

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Stickler syndrome type 1

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

clinical testing

Invitae

Feb 01, 2024

- -

Type II Collagenopathies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

DANN

Benign

0.31

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