Variant rs41317929 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.1681-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,612,190 control chromosomes in the GnomAD database, including 3,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 256 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3471 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.616

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:

COL2A1 (HGNC:):

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=-0.77).

BP6

Variant 12-47985625-C-T is Benign according to our data. Variant chr12-47985625-C-T is described in ClinVar as [Benign]. Clinvar id is 258215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47985625-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 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.1681-38G>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.1681-38G>A	intron_variant	1	NM_001844.5	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.1474-38G>A	intron_variant	1		ENSP00000338213.6	P02458-1
COL2A1	ENST00000493991.5 linkuse as main transcript	n.605-38G>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0505

AC:

7678

AN:

152090

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0864

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0732

Gnomad OTH

AF:

0.0446

GnomAD3 exomes

AF:

0.0475

AC:

11898

AN:

250578

Hom.:

425

AF XY:

0.0469

AC XY:

6353

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.0253

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.0726

Gnomad OTH exome

AF:

0.0474

GnomAD4 exome

AF:

0.0639

AC:

93277

AN:

1459982

Hom.:

3471

Cov.:

AF XY:

0.0623

AC XY:

45255

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.0196

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.0741

Gnomad4 OTH exome

AF:

0.0540

GnomAD4 genome

AF:

0.0505

AC:

7681

AN:

152208

Hom.:

256

Cov.:

AF XY:

0.0499

AC XY:

3714

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.0864

Gnomad4 NFE

AF:

0.0732

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0611

Hom.:

Bravo

AF:

0.0436

Asia WGS

AF:

0.0100

AC:

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 26, 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

-0.77

CADD

Benign

2.2

DANN

Benign

0.80

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