rs1034762

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001844.5(COL2A1):c.654+15T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,611,240 control chromosomes in the GnomAD database, including 536,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47419 hom., cov: 31)

Exomes 𝑓: 0.81 ( 488983 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.92

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=-0.84).

BP6

Variant 12-47995860-A-C is Benign according to our data. Variant chr12-47995860-A-C is described in ClinVar as [Benign]. Clinvar id is 258243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47995860-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5 link	c.654+15T>G		intron_variant	Intron 9 of 53	ENST00000380518.8	NP_001835.3	P02458-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8 link	c.654+15T>G		intron_variant	Intron 9 of 53	1	NM_001844.5	ENSP00000369889.3		P02458-2
COL2A1	ENST00000337299.7 link	c.447+15T>G		intron_variant	Intron 8 of 52	1		ENSP00000338213.6		P02458-1

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119283

AN:

151958

Hom.:

47385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.788

GnomAD3 exomes

AF:

0.738

AC:

185608

AN:

251476

Hom.:

70918

AF XY:

0.745

AC XY:

101323

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.783

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.791

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.759

Gnomad NFE exome

AF:

0.846

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.813

AC:

1186578

AN:

1459164

Hom.:

488983

Cov.:

AF XY:

0.810

AC XY:

588402

AN XY:

726142

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.797

Gnomad4 EAS exome

AF:

0.494

Gnomad4 SAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.852

Gnomad4 OTH exome

AF:

0.797

GnomAD4 genome

AF:

0.785

AC:

119368

AN:

152076

Hom.:

47419

Cov.:

AF XY:

0.774

AC XY:

57520

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.783

Gnomad4 AMR

AF:

0.660

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.515

Gnomad4 SAS

AF:

0.645

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.847

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.811

Hom.:

28768

Bravo

AF:

0.775

Asia WGS

AF:

0.593

AC:

2067

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Stickler syndrome type 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.40

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