Variant chr12-47995953-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001844.5(COL2A1):c.610-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,583,026 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 59 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0850

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 12-47995953-A-G is Benign according to our data. Variant chr12-47995953-A-G is described in ClinVar as [Benign]. Clinvar id is 258242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00215 (327/152238) while in subpopulation EAS AF= 0.0514 (266/5176). AF 95% confidence interval is 0.0463. There are 7 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5 linkuse as main transcript	c.610-34T>C		intron_variant		ENST00000380518.8	NP_001835.3	P02458-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.610-34T>C		intron_variant		1	NM_001844.5	ENSP00000369889.3		P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.403-34T>C		intron_variant		1		ENSP00000338213.6		P02458-1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00459

AC:

1153

AN:

251012

Hom.:

AF XY:

0.00419

AC XY:

568

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0608

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00139

AC:

1992

AN:

1430788

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

978

AN XY:

714112

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000270

Gnomad4 EAS exome

AF:

0.0416

Gnomad4 SAS exome

AF:

0.000490

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000314

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152238

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0514

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000584

Hom.:

Bravo

AF:

0.00261

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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