rs72481820

Variant names:

• chr18-69867406-C-T
• rs72481820
• NM_001303618.2:c.836G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 18 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 -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.

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.836G>A	p.Arg279Lys	missense	Exon 5 of 6	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.836G>A	p.Arg279Lys	missense	Exon 6 of 7	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.371G>A	p.Arg124Lys	missense	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.836G>A	p.Arg279Lys	missense	Exon 5 of 6	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.836G>A	p.Arg279Lys	missense	Exon 6 of 7	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.371G>A	p.Arg124Lys	missense	Exon 4 of 5	ENSP00000464084.1	J3QR77

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

GnomAD2 exomes AF: 0.0752 AC: 18844 AN: 250482 AF XY: 0.0739

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 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

African (AFR) AF: 0.0797 AC: 2583 AN: 32428

American (AMR) AF: 0.0913 AC: 4062 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.0731 AC: 1886 AN: 25786

East Asian (EAS) AF: 0.0498 AC: 1965 AN: 39468

South Asian (SAS) AF: 0.0716 AC: 6096 AN: 85104

European-Finnish (FIN) AF: 0.111 AC: 5859 AN: 52796

Middle Eastern (MID) AF: 0.102 AC: 578 AN: 5666

European-Non Finnish (NFE) AF: 0.0674 AC: 71630 AN: 1062440

Other (OTH) AF: 0.0722 AC: 4230 AN: 58558

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

African (AFR) AF: 0.0859 AC: 3569 AN: 41528

American (AMR) AF: 0.0828 AC: 1267 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5188

South Asian (SAS) AF: 0.0694 AC: 335 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0714 AC: 4855 AN: 68010

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0715 Hom.: 823

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 v4.9

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
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.47
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.026
Sift	Benign	0.45	T
Sift4G	Benign	0.27	T
Polyphen		0.23	B
Vest4		0.13
MPC		0.21
ClinPred		0.0021	T
GERP RS		2.8
Varity_R		0.068
gMVP		0.45
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

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