rs72481820

Positions:

• chr18-69867406-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.836G>A​(p.Arg279Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 1,558,970 control chromosomes in the GnomAD database, including 4,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (477 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3818 hom.)
• Consequence: CD226 NM_001303618.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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 (MetaRNN=0.0016562045).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.836G>A	p.Arg279Lys	missense_variant	5/6	ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.836G>A	p.Arg279Lys	missense_variant	5/6	1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 11867 AN: 152094 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.0757

GnomAD3 exomes AF: 0.0752 AC: 18844 AN: 250482 Hom.: 806 AF XY: 0.0739 AC XY: 10011 AN XY: 135446

Gnomad AFR exome AF: 0.0827

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.0808

Gnomad EAS exome AF: 0.0164

Gnomad SAS exome AF: 0.0734

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0721

Gnomad OTH exome AF: 0.0801

GnomAD4 exome AF: 0.0703 AC: 98889 AN: 1406758 Hom.: 3818 Cov.: 25 AF XY: 0.0704 AC XY: 49512 AN XY: 703196

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.0913

Gnomad4 ASJ exome AF: 0.0731

Gnomad4 EAS exome AF: 0.0498

Gnomad4 SAS exome AF: 0.0716

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0674

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0781 AC: 11883 AN: 152212 Hom.: 477 Cov.: 32 AF XY: 0.0788 AC XY: 5860 AN XY: 74406

Gnomad4 AFR AF: 0.0859

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.0759

Alfa AF: 0.0708 Hom.: 599

Bravo AF: 0.0770

TwinsUK AF: 0.0715 AC: 265

ALSPAC AF: 0.0714 AC: 275

ESP6500AA AF: 0.0754 AC: 332

ESP6500EA AF: 0.0723 AC: 622

ExAC AF: 0.0742 AC: 9005

Asia WGS AF: 0.0660 AC: 227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.071	T;T;T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.39	.;.;T;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.;L
MutationTaster	Benign	0.93	P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.030	N;.;.;.
REVEL	Benign	0.026
Sift	Benign	0.45	T;.;.;.
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.23	B;.;.;B
Vest4		0.13
MPC		0.21
ClinPred		0.0021	T
GERP RS		2.8
Varity_R		0.068
gMVP		0.45

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: rs72481820; hg19: chr18-67534642; COSMIC: COSV54612168;