12-48001040-G-T

Position:

• chr12-48001040-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.86-915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,214 control chromosomes in the GnomAD database, including 8,089 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 0.30 (8089 hom., cov: 33)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.86-915C>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.86-915C>A		intron_variant		1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.86-2609C>A		intron_variant		1		ENSP00000338213.6
COL2A1	ENST00000474996.6	n.268C>A		non_coding_transcript_exon_variant	2/8	3
COL2A1	ENST00000490609.2	n.319-915C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45637 AN: 152050 Hom.: 8078 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.217 AC: 10 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.225 AC XY: 9 AN XY: 40

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.300 AC: 45680 AN: 152168 Hom.: 8089 Cov.: 33 AF XY: 0.295 AC XY: 21954 AN XY: 74414

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.262

Alfa AF: 0.236 Hom.: 5915

Bravo AF: 0.302

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.85

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: rs954326; hg19: chr12-48394823;