rs72481819

Variant names:

• chr18-69867396-C-T
• rs72481819
• NM_001303618.2:c.846G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001303618.2(CD226):​c.846G>A​(p.Glu282Glu) 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.846G>A	p.Glu282Glu	synonymous	Exon 5 of 6	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.846G>A	p.Glu282Glu	synonymous	Exon 6 of 7	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.381G>A	p.Glu127Glu	synonymous	Exon 4 of 5	NP_001290548.1	J3QR77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.846G>A	p.Glu282Glu	synonymous	Exon 5 of 6	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.846G>A	p.Glu282Glu	synonymous	Exon 6 of 7	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.381G>A	p.Glu127Glu	synonymous	Exon 4 of 5	ENSP00000464084.1	J3QR77

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

GnomAD2 exomes AF: 0.0493 AC: 12359 AN: 250712 AF XY: 0.0491

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 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

African (AFR) AF: 0.0125 AC: 406 AN: 32532

American (AMR) AF: 0.0304 AC: 1354 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 969 AN: 25816

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39466

South Asian (SAS) AF: 0.00927 AC: 791 AN: 85340

European-Finnish (FIN) AF: 0.119 AC: 6274 AN: 52892

Middle Eastern (MID) AF: 0.0100 AC: 57 AN: 5684

European-Non Finnish (NFE) AF: 0.0685 AC: 72850 AN: 1063476

Other (OTH) AF: 0.0537 AC: 3150 AN: 58624

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

African (AFR) AF: 0.0159 AC: 660 AN: 41502

American (AMR) AF: 0.0426 AC: 652 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00851 AC: 41 AN: 4820

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10572

Middle Eastern (MID) AF: 0.0207 AC: 6 AN: 290

European-Non Finnish (NFE) AF: 0.0697 AC: 4737 AN: 67950

Other (OTH) AF: 0.0465 AC: 98 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.23
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72481819; hg19: chr18-67534632;