dbSNP rs72481819: CD226:p.Glu282Glu (chr18-69867396-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

Publications

9 publications found

Variant links:

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]

CD226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.846G>A	p.Glu282Glu	synonymous_variant	Exon 5 of 6	ENST00000582621.6	NP_001290547.1	Q15762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6 link	c.846G>A	p.Glu282Glu	synonymous_variant	Exon 5 of 6	1	NM_001303618.2	ENSP00000461947.1		Q15762

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

7707

AN:

151980

Hom.:

301

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0595

AC XY:

41903

AN XY:

704000

show subpopulations

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:

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:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0685

AC:

72850

AN:

1063476

Other (OTH)

AF:

0.0537

AC:

3150

AN:

58624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

3217

6433

9650

12866

16083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2560

5120

7680

10240

12800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0506

AC:

7703

AN:

152098

Hom.:

301

Cov.:

AF XY:

0.0532

AC XY:

3954

AN XY:

74348

show subpopulations

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:

AN:

5182

South Asian (SAS)

AF:

0.00851

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.130

AC:

1373

AN:

10572

Middle Eastern (MID)

AF:

0.0207

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0697

AC:

4737

AN:

67950

Other (OTH)

AF:

0.0465

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

374

748

1123

1497

1871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0566

Hom.:

179

Bravo

AF:

0.0424

Asia WGS

AF:

0.00636

AC:

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

(source)

DANN

Benign

0.23

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over