Genetic Variant NM_001303618.2:c.*524G>T (chr18-69863790-C-A) – 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.*524G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,456 control chromosomes in the GnomAD database, including 10,044 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 0.36 ( 9992 hom., cov: 32)

Exomes 𝑓: 0.42 ( 52 hom. )

Consequence

CD226
NM_001303618.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

19 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.*524G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000582621.6	NP_001290547.1	Q15762

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD226	ENST00000582621.6 link	c.*524G>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_001303618.2	ENSP00000461947.1	Q15762
CD226	ENST00000280200.8 link	c.*524G>T	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000280200.4	Q15762
CD226	ENST00000581982.5 link	c.*524G>T	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000464084.1	J3QR77
CD226	ENST00000578928.1 link	n.110-21395G>T	intron_variant	Intron 1 of 3	4		ENSP00000463152.1	J3QKM7

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54276

AN:

151890

Hom.:

9981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.424

AC:

190

AN:

448

Hom.:

Cov.:

AF XY:

0.443

AC XY:

108

AN XY:

244

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AF:

0.385

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.833

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.414

AC:

158

AN:

382

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.357

AC:

54324

AN:

152008

Hom.:

9992

Cov.:

AF XY:

0.352

AC XY:

26164

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.312

AC:

12942

AN:

41458

American (AMR)

AF:

0.343

AC:

5234

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1294

AN:

3470

East Asian (EAS)

AF:

0.242

AC:

1252

AN:

5174

South Asian (SAS)

AF:

0.408

AC:

1964

AN:

4818

European-Finnish (FIN)

AF:

0.295

AC:

3112

AN:

10554

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27119

AN:

67944

Other (OTH)

AF:

0.391

AC:

826

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1766

3532

5298

7064

8830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.381

Hom.:

3946

Bravo

AF:

0.362

Asia WGS

AF:

0.316

AC:

1102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.34

(source)

DANN

Benign

0.36

PhyloP100

-1.8

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