Variant 12-47986248-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_StrongBA1

The NM_001844.5(COL2A1):c.1527+88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 934,790 control chromosomes in the GnomAD database, including 103,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17069 hom., cov: 32)

Exomes 𝑓: 0.47 ( 86312 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.747

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 12-47986248-A-G is Benign according to our data. Variant chr12-47986248-A-G is described in ClinVar as [Benign]. Clinvar id is 585507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 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.1527+88T>C		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.1527+88T>C	intron_variant	1	NM_001844.5	ENSP00000369889	P1	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.1320+88T>C	intron_variant	1		ENSP00000338213		P02458-1
COL2A1	ENST00000493991.5 linkuse as main transcript	n.451+88T>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71511

AN:

151862

Hom.:

17061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.469

GnomAD4 exome

AF:

0.466

AC:

364687

AN:

782810

Hom.:

86312

AF XY:

0.468

AC XY:

191012

AN XY:

408306

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.475

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.473

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.471

AC:

71540

AN:

151980

Hom.:

17069

Cov.:

AF XY:

0.467

AC XY:

34710

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.382

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.472

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.463

Hom.:

33508

Bravo

AF:

0.466

Asia WGS

AF:

0.469

AC:

1629

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 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	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.83

DANN

Benign

0.27

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