Variant 12-47973271-G-A 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.*136C>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 0.0669 in 1,171,608 control chromosomes in the GnomAD database, including 3,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 308 hom., cov: 32)

Exomes 𝑓: 0.068 ( 2770 hom. )

Consequence

COL2A1
NM_001844.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.717

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 12-47973271-G-A is Benign according to our data. Variant chr12-47973271-G-A is described in ClinVar as [Benign]. Clinvar id is 308898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47973271-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0775 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.*136C>T		3_prime_UTR_variant	54/54	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.*136C>T		3_prime_UTR_variant	54/54	1	NM_001844.5	ENSP00000369889	P1	P02458-2
COL2A1	ENST00000493991.5 linkuse as main transcript	n.3686C>T		non_coding_transcript_exon_variant	37/37	2

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8617

AN:

152068

Hom.:

308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.0925

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.0464

GnomAD4 exome

AF:

0.0685

AC:

69792

AN:

1019422

Hom.:

2770

Cov.:

AF XY:

0.0667

AC XY:

35020

AN XY:

524824

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0208

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.0807

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0566

AC:

8619

AN:

152186

Hom.:

308

Cov.:

AF XY:

0.0565

AC XY:

4204

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0925

Gnomad4 NFE

AF:

0.0793

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0718

Hom.:

Bravo

AF:

0.0504

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.48

CADD

Benign

9.7

DANN

Benign

0.81

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