Variant rs1635550 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.1888-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,574,222 control chromosomes in the GnomAD database, including 507,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42882 hom., cov: 32)

Exomes 𝑓: 0.81 ( 465052 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.817

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=-0.88).

BP6

Variant 12-47984187-A-G is Benign according to our data. Variant chr12-47984187-A-G is described in ClinVar as [Benign]. Clinvar id is 258219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47984187-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5 link	c.1888-47T>C		intron_variant		ENST00000380518.8	NP_001835.3	P02458-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL2A1	ENST00000380518.8 link	c.1888-47T>C	intron_variant	1	NM_001844.5	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7 link	c.1681-47T>C	intron_variant	1		ENSP00000338213.6	P02458-1
COL2A1	ENST00000493991.5 link	n.812-47T>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.745

AC:

113276

AN:

151952

Hom.:

42857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.796

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.757

GnomAD3 exomes

AF:

0.740

AC:

164232

AN:

221870

Hom.:

62100

AF XY:

0.752

AC XY:

89947

AN XY:

119534

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.625

Gnomad SAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.831

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.805

AC:

1145485

AN:

1422152

Hom.:

465052

Cov.:

AF XY:

0.805

AC XY:

569529

AN XY:

707216

show subpopulations

Gnomad4 AFR exome

AF:

0.634

Gnomad4 AMR exome

AF:

0.559

Gnomad4 ASJ exome

AF:

0.779

Gnomad4 EAS exome

AF:

0.609

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.753

Gnomad4 NFE exome

AF:

0.836

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.745

AC:

113344

AN:

152070

Hom.:

42882

Cov.:

AF XY:

0.740

AC XY:

55043

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.671

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.628

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.755

Gnomad4 NFE

AF:

0.834

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.805

Hom.:

48780

Bravo

AF:

0.732

Asia WGS

AF:

0.640

AC:

2229

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 14, 2018	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. -
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

-0.88

CADD

Benign

0.16

DANN

Benign

0.30

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