chr12-47973403-G-A

Position:

chr12-47973403-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001844.5(COL2A1):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,614,058 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 122 hom. )

Consequence

COL2A1
NM_001844.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.46

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 12-47973403-G-A is Benign according to our data. Variant chr12-47973403-G-A is described in ClinVar as [Benign]. Clinvar id is 308902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47973403-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 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.*4C>T		3_prime_UTR_variant	54/54	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	54/54	1	NM_001844.5	ENSP00000369889	P1	P02458-2
COL2A1	ENST00000493991.5 linkuse as main transcript	n.3554C>T	non_coding_transcript_exon_variant	37/37	2
COL2A1	ENST00000337299.7 linkuse as main transcript		downstream_gene_variant		1		ENSP00000338213		P02458-1

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3233

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00967

AC:

2431

AN:

251494

Hom.:

AF XY:

0.00840

AC XY:

1142

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0674

Gnomad AMR exome

AF:

0.00650

Gnomad ASJ exome

AF:

0.0342

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00307

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00511

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.00608

AC:

8891

AN:

1461890

Hom.:

122

Cov.:

AF XY:

0.00580

AC XY:

4220

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.00693

Gnomad4 ASJ exome

AF:

0.0342

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.00386

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.0213

AC:

3245

AN:

152168

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1581

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0626

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00605

EpiControl

AF:

0.00670

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 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. -

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. -

Type II Collagenopathies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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