12-47990339-T-C

Position:

• chr12-47990339-T-C

Variant summary

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

The NM_001844.5(COL2A1):​c.1024-534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,128 control chromosomes in the GnomAD database, including 18,928 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 0.49 (18928 hom., cov: 33)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.1024-534A>G		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.1024-534A>G		intron_variant		1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.817-534A>G		intron_variant		1		ENSP00000338213.6

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75162 AN: 152008 Hom.: 18913 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.494 AC: 75206 AN: 152128 Hom.: 18928 Cov.: 33 AF XY: 0.491 AC XY: 36551 AN XY: 74372

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.485

Alfa AF: 0.477 Hom.: 22862

Bravo AF: 0.494

Asia WGS AF: 0.471 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.37

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: rs1793923; hg19: chr12-48384122;