Variant rs1635560 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.4317+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,520 control chromosomes in the GnomAD database, including 44,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3795 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40409 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.37

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=-0.9).

BP6

Variant 12-47974046-G-A is Benign according to our data. Variant chr12-47974046-G-A is described in ClinVar as [Benign]. Clinvar id is 258240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 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.4317+43C>T		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.4317+43C>T	intron_variant	1	NM_001844.5	ENSP00000369889	P1	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.4110+43C>T	intron_variant	1		ENSP00000338213		P02458-1
COL2A1	ENST00000493991.5 linkuse as main transcript	n.3403+43C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33630

AN:

151992

Hom.:

3790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.228

GnomAD3 exomes

AF:

0.221

AC:

55094

AN:

249444

Hom.:

6465

AF XY:

0.229

AC XY:

30897

AN XY:

134998

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.233

AC:

340967

AN:

1461410

Hom.:

40409

Cov.:

AF XY:

0.237

AC XY:

172112

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.221

AC:

33669

AN:

152110

Hom.:

3795

Cov.:

AF XY:

0.218

AC XY:

16224

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.238

Hom.:

4375

Bravo

AF:

0.218

Asia WGS

AF:

0.236

AC:

818

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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.90

CADD

Benign

0.26

DANN

Benign

0.50

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