18-69898227-C-T

Position:

• chr18-69898227-C-T

Variant summary

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

The NM_001303618.2(CD226):​c.383-2182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,992 control chromosomes in the GnomAD database, including 3,171 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 0.20 (3171 hom., cov: 32)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

CD226 (HGNC:16961): (CD226 molecule) This gene encodes a glycoprotein expressed on the surface of NK cells, platelets, monocytes and a subset of T cells. It is a member of the Ig-superfamily containing 2 Ig-like domains of the V-set. The protein mediates cellular adhesion of platelets and megakaryocytic cells to vascular endothelial cells. The protein also plays a role in megakaryocytic cell maturation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.383-2182G>A		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.383-2182G>A		intron_variant		1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29840 AN: 151874 Hom.: 3167 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.196 AC: 29846 AN: 151992 Hom.: 3171 Cov.: 32 AF XY: 0.196 AC XY: 14546 AN XY: 74278

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.217

Alfa AF: 0.201 Hom.: 1890

Bravo AF: 0.191

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.59

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: rs17208329; hg19: chr18-67565463;