Genetic Variant CD226:c.*6904C>A (chr18-69857410-G-T) – 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.*6904C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,028 control chromosomes in the GnomAD database, including 10,666 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 0.37 ( 10666 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

CD226
NM_001303618.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

Publications

7 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 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
CD226	NM_001303618.2	MANE Select	c.*6904C>A	3_prime_UTR	Exon 6 of 6	NP_001290547.1
CD226	NM_006566.4		c.*6904C>A	3_prime_UTR	Exon 7 of 7	NP_006557.2
CD226	NM_001303619.2		c.*6904C>A	3_prime_UTR	Exon 5 of 5	NP_001290548.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CD226	ENST00000582621.6	TSL:1 MANE Select	c.*6904C>A	3_prime_UTR	Exon 6 of 6	ENSP00000461947.1
CD226	ENST00000280200.8	TSL:1	c.*6904C>A	3_prime_UTR	Exon 7 of 7	ENSP00000280200.4
CD226	ENST00000578928.1	TSL:4	n.110-15015C>A	intron	N/A	ENSP00000463152.1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56356

AN:

151906

Hom.:

10652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.371

AC:

56411

AN:

152024

Hom.:

10666

Cov.:

AF XY:

0.366

AC XY:

27168

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.351

AC:

14546

AN:

41468

American (AMR)

AF:

0.349

AC:

5326

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1298

AN:

3466

East Asian (EAS)

AF:

0.243

AC:

1253

AN:

5162

South Asian (SAS)

AF:

0.409

AC:

1971

AN:

4822

European-Finnish (FIN)

AF:

0.308

AC:

3256

AN:

10568

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27330

AN:

67962

Other (OTH)

AF:

0.403

AC:

852

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1840

3680

5521

7361

9201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.384

Hom.:

8254

Bravo

AF:

0.377

Asia WGS

AF:

0.321

AC:

1121

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.69

(source)

DANN

Benign

0.64

PhyloP100

-0.097

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over