rs72481819

Positions:

• chr18-69867396-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001303618.2(CD226):​c.846G>A​(p.Glu282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,560,522 control chromosomes in the GnomAD database, including 3,480 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 0.051 (301 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3179 hom.)
• Consequence: CD226 NM_001303618.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.156 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.846G>A	p.Glu282=	synonymous_variant	5/6	ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.846G>A	p.Glu282=	synonymous_variant	5/6	1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.0507 AC: 7707 AN: 151980 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0470

GnomAD3 exomes AF: 0.0493 AC: 12359 AN: 250712 Hom.: 501 AF XY: 0.0491 AC XY: 6648 AN XY: 135520

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.0279

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00971

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.0671

Gnomad OTH exome AF: 0.0550

GnomAD4 exome AF: 0.0610 AC: 85856 AN: 1408424 Hom.: 3179 Cov.: 25 AF XY: 0.0595 AC XY: 41903 AN XY: 704000

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0375

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00927

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0685

Gnomad4 OTH exome AF: 0.0537

GnomAD4 genome AF: 0.0506 AC: 7703 AN: 152098 Hom.: 301 Cov.: 32 AF XY: 0.0532 AC XY: 3954 AN XY: 74348

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0426

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0697

Gnomad4 OTH AF: 0.0465

Alfa AF: 0.0566 Hom.: 179

Bravo AF: 0.0424

Asia WGS AF: 0.00636 AC: 22 AN: 3474

EpiCase AF: 0.0602

EpiControl AF: 0.0603

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs72481819; hg19: chr18-67534632;