Genetic Variant COL2A1:c.292+258G>A (chr12-47999661-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001844.5(COL2A1):c.292+258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 22599 hom., cov: 17)

Exomes 𝑓: 0.81 ( 12494 hom. )

Consequence

COL2A1
NM_001844.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.266

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=-0.78).

BP6

Variant 12-47999661-C-T is Benign according to our data. Variant chr12-47999661-C-T is described in ClinVar as [Benign]. Clinvar id is 671012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5 link	c.292+258G>A		intron_variant	Intron 2 of 53	ENST00000380518.8	NP_001835.3	P02458-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL2A1	ENST00000380518.8 link	c.292+258G>A	intron_variant	Intron 2 of 53	1	NM_001844.5	ENSP00000369889.3	P02458-2
COL2A1	ENST00000337299.7 link	c.86-1230G>A	intron_variant	Intron 1 of 52	1		ENSP00000338213.6	P02458-1
COL2A1	ENST00000474996.6 link	n.530+258G>A	intron_variant	Intron 3 of 7	3
COL2A1	ENST00000490609.2 link	n.*36G>A	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

75306

AN:

114826

Hom.:

22606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.685

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.663

GnomAD4 exome

AF:

0.806

AC:

30937

AN:

38380

Hom.:

12494

Cov.:

AF XY:

0.803

AC XY:

15802

AN XY:

19676

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.794

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.853

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.822

Gnomad4 OTH exome

AF:

0.794

GnomAD4 genome

AF:

0.656

AC:

75309

AN:

114854

Hom.:

22599

Cov.:

AF XY:

0.652

AC XY:

35603

AN XY:

54588

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.670

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.605

Gnomad4 SAS

AF:

0.673

Gnomad4 FIN

AF:

0.691

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.662

Alfa

AF:

0.587

Hom.:

3419

Bravo

AF:

0.522

Asia WGS

AF:

0.489

AC:

1685

AN:

3444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.9

DANN

Benign

0.70

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