rs2248990

Positions:

• chr12-47995047-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001844.5(COL2A1):​c.762+208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,024 control chromosomes in the GnomAD database, including 24,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (24107 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-47995047-C-T is Benign according to our data. Variant chr12-47995047-C-T is described in ClinVar as [Benign]. Clinvar id is 677853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.762+208G>A		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.762+208G>A		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.555+208G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83064 AN: 151906 Hom.: 24098 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.547 AC: 83117 AN: 152024 Hom.: 24107 Cov.: 32 AF XY: 0.540 AC XY: 40124 AN XY: 74302

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.567

Alfa AF: 0.594 Hom.: 3449

Bravo AF: 0.532

Asia WGS AF: 0.415 AC: 1447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs2248990; hg19: chr12-48388830;