rs17801742

Positions:

chr12-47983086-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001844.5(COL2A1):c.2094+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,613,540 control chromosomes in the GnomAD database, including 3,471 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 232 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3239 hom. )

Consequence

COL2A1
NM_001844.5 splice_region, intron

Scores

Splicing: ADA: 0.00008144

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.570

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:

COL2A1 (HGNC:):

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=-0.71).

BP6

Variant 12-47983086-T-C is Benign according to our data. Variant chr12-47983086-T-C is described in ClinVar as [Benign]. Clinvar id is 258223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47983086-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5 linkuse as main transcript	c.2094+7A>G		splice_region_variant, intron_variant		ENST00000380518.8	NP_001835.3	P02458-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.2094+7A>G	splice_region_variant, intron_variant	1	NM_001844.5	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.1887+7A>G	splice_region_variant, intron_variant	1		ENSP00000338213.6	P02458-1
COL2A1	ENST00000483376.1 linkuse as main transcript	n.272+7A>G	splice_region_variant, intron_variant	5
COL2A1	ENST00000493991.5 linkuse as main transcript	n.1018+7A>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7558

AN:

152012

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0714

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0454

AC:

11332

AN:

249550

Hom.:

361

AF XY:

0.0450

AC XY:

6081

AN XY:

135036

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.0201

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0753

Gnomad NFE exome

AF:

0.0693

Gnomad OTH exome

AF:

0.0469

GnomAD4 exome

AF:

0.0622

AC:

90930

AN:

1461410

Hom.:

3239

Cov.:

AF XY:

0.0607

AC XY:

44125

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.0218

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0760

Gnomad4 NFE exome

AF:

0.0722

Gnomad4 OTH exome

AF:

0.0535

GnomAD4 genome

AF:

0.0497

AC:

7559

AN:

152130

Hom.:

232

Cov.:

AF XY:

0.0492

AC XY:

3659

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.0292

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0121

Gnomad4 FIN

AF:

0.0772

Gnomad4 NFE

AF:

0.0713

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0577

Hom.:

387

Bravo

AF:

0.0441

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0564

EpiControl

AF:

0.0614

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Stickler syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Type II Collagenopathies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000081

dbscSNV1_RF

Benign

0.0

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