12-47991793-A-G

Position:

• chr12-47991793-A-G

Variant summary

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

The NM_001844.5(COL2A1):​c.1023+1085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,130 control chromosomes in the GnomAD database, including 49,174 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 0.80 (49174 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.1023+1085T>C		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.1023+1085T>C		intron_variant		1	NM_001844.5	ENSP00000369889	P1
COL2A1	ENST00000337299.7	c.816+1085T>C		intron_variant		1		ENSP00000338213

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121762 AN: 152012 Hom.: 49142 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.801 AC: 121845 AN: 152130 Hom.: 49174 Cov.: 32 AF XY: 0.793 AC XY: 59004 AN XY: 74380

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.799

Alfa AF: 0.826 Hom.: 21453

Bravo AF: 0.792

Asia WGS AF: 0.652 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.63

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: rs917055; hg19: chr12-48385576;