Genetic Variant CD226:c.831-63T>C (chr18-69867474-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001303618.2(CD226):c.831-63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,062,186 control chromosomes in the GnomAD database, including 812 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 0.0096 ( 63 hom., cov: 32)

Exomes 𝑓: 0.012 ( 749 hom. )

Consequence

CD226
NM_001303618.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD226	NM_001303618.2	MANE Select	c.831-63T>C	intron	N/A	NP_001290547.1	Q15762
CD226	NM_006566.4		c.831-63T>C	intron	N/A	NP_006557.2	Q15762
CD226	NM_001303619.2		c.366-63T>C	intron	N/A	NP_001290548.1	J3QR77

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD226	ENST00000582621.6	TSL:1 MANE Select	c.831-63T>C	intron	N/A	ENSP00000461947.1	Q15762
CD226	ENST00000280200.8	TSL:1	c.831-63T>C	intron	N/A	ENSP00000280200.4	Q15762
CD226	ENST00000581982.5	TSL:1	c.366-63T>C	intron	N/A	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes

AF:

0.00957

AC:

1456

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.0119

AC:

10843

AN:

909900

Hom.:

749

AF XY:

0.0106

AC XY:

5064

AN XY:

476774

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

23012

American (AMR)

AF:

0.0848

AC:

3716

AN:

43834

Ashkenazi Jewish (ASJ)

AF:

0.000220

AC:

AN:

22686

East Asian (EAS)

AF:

0.164

AC:

6132

AN:

37364

South Asian (SAS)

AF:

0.00146

AC:

110

AN:

75138

European-Finnish (FIN)

AF:

0.000421

AC:

AN:

47450

Middle Eastern (MID)

AF:

0.000635

AC:

AN:

4722

European-Non Finnish (NFE)

AF:

0.000504

AC:

309

AN:

613306

Other (OTH)

AF:

0.0116

AC:

490

AN:

42388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

492

984

1476

1968

2460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00964

AC:

1468

AN:

152286

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

771

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41570

American (AMR)

AF:

0.0373

AC:

570

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.133

AC:

689

AN:

5172

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68024

Other (OTH)

AF:

0.00996

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.000445

Hom.:

Bravo

AF:

0.0156

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.99

(source)

DANN

Benign

0.38

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over