12-48001319-T-G

Variant names:

• chr12-48001319-T-G
• rs1635529
• NM_001844.5:c.86-1194A>C

Variant summary

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

The NM_001844.5(COL2A1):​c.86-1194A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,252 control chromosomes in the GnomAD database, including 46,204 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 0.77 (46204 hom., cov: 35)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.86-1194A>C		intron_variant	Intron 1 of 53	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.86-1194A>C		intron_variant	Intron 1 of 53	1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.86-2888A>C		intron_variant	Intron 1 of 52	1		ENSP00000338213.6
COL2A1	ENST00000474996.6	n.214-225A>C		intron_variant	Intron 1 of 7	3
COL2A1	ENST00000490609.2	n.319-1194A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117890 AN: 152134 Hom.: 46180 Cov.: 35

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.775 AC: 117965 AN: 152252 Hom.: 46204 Cov.: 35 AF XY: 0.767 AC XY: 57110 AN XY: 74432

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.781

Alfa AF: 0.764 Hom.: 2684

Bravo AF: 0.762

Asia WGS AF: 0.657 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.66

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: rs1635529; hg19: chr12-48395102;