chr12-48002667-G-T

Position:

• chr12-48002667-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001844.5(COL2A1):​c.85+1570C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,230 control chromosomes in the GnomAD database, including 44,704 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44696 hom., cov: 34)
  • Exomes 𝑓: 0.86 (8 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.85+1570C>A		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.85+1570C>A		intron_variant		1	NM_001844.5	ENSP00000369889.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115739 AN: 152090 Hom.: 44676 Cov.: 34

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.864 AC: 19 AN: 22 Hom.: 8 Cov.: 0 AF XY: 0.889 AC XY: 16 AN XY: 18

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

GnomAD4 genome AF: 0.761 AC: 115808 AN: 152208 Hom.: 44696 Cov.: 34 AF XY: 0.754 AC XY: 56107 AN XY: 74404

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.767

Alfa AF: 0.824 Hom.: 85345

Bravo AF: 0.747

Asia WGS AF: 0.657 AC: 2286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.67

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: rs1793933; hg19: chr12-48396450;