Variant rs3829735 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.2193+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,581,386 control chromosomes in the GnomAD database, including 945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 68 hom., cov: 33)

Exomes 𝑓: 0.012 ( 877 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.50

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:

LOC105369752 (HGNC:):

LOC105369752 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=-0.83).

BP6

Variant 12-47982816-C-T is Benign according to our data. Variant chr12-47982816-C-T is described in ClinVar as [Benign]. Clinvar id is 258224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 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.2193+32G>A		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.2193+32G>A	intron_variant	1	NM_001844.5	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.1986+32G>A	intron_variant	1		ENSP00000338213.6	P02458-1
COL2A1	ENST00000483376.1 linkuse as main transcript	n.371+32G>A	intron_variant	5
COL2A1	ENST00000493991.5 linkuse as main transcript	n.1117+32G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1753

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00883

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0254

AC:

6193

AN:

243420

Hom.:

350

AF XY:

0.0301

AC XY:

3986

AN XY:

132480

show subpopulations

Gnomad AFR exome

AF:

0.00967

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00890

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0000604

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0120

AC:

17093

AN:

1429088

Hom.:

877

Cov.:

AF XY:

0.0151

AC XY:

10788

AN XY:

712968

show subpopulations

Gnomad4 AFR exome

AF:

0.00856

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.00951

Gnomad4 EAS exome

AF:

0.0955

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.000108

Gnomad4 NFE exome

AF:

0.00148

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0115

AC:

1750

AN:

152298

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1053

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.0996

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00725

Hom.:

Bravo

AF:

0.00997

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.057

DANN

Benign

0.49

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