Variant chr12-47986181-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+155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,752 control chromosomes in the GnomAD database, including 16,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16988 hom., cov: 32)

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0350

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=-0.87).

BP6

Variant 12-47986181-A-G is Benign according to our data. Variant chr12-47986181-A-G is described in ClinVar as [Benign]. Clinvar id is 585505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5 linkuse as main transcript	c.1527+155T>C		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8 linkuse as main transcript	c.1527+155T>C	intron_variant	1	NM_001844.5	P1	P02458-2
COL2A1	ENST00000337299.7 linkuse as main transcript	c.1320+155T>C	intron_variant	1			P02458-1
COL2A1	ENST00000493991.5 linkuse as main transcript	n.451+155T>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71317

AN:

151632

Hom.:

16976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.470

AC:

71352

AN:

151752

Hom.:

16988

Cov.:

AF XY:

0.466

AC XY:

34558

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.481

Gnomad4 FIN

AF:

0.425

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.468

Alfa

AF:

0.459

Hom.:

1965

Bravo

AF:

0.467

Asia WGS

AF:

0.465

AC:

1616

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.6

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