Genetic Variant NM_001303618.2: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.831-63T>C		intron_variant	Intron 4 of 5	ENST00000582621.6	NP_001290547.1	Q15762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6 link	c.831-63T>C		intron_variant	Intron 4 of 5	1	NM_001303618.2	ENSP00000461947.1		Q15762

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over