Genetic Variant CD226:p.Ser227Asn (chr18-69895748-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001303618.2(CD226):c.680G>A(p.Ser227Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S227I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD226
NM_001303618.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.396

Publications

0 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:

ENSG00000304227 (HGNC:):

ENSG00000304227 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083902955).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
CD226	NM_001303618.2	MANE Select	c.680G>A	p.Ser227Asn	missense	Exon 3 of 6	NP_001290547.1	Q15762
CD226	NM_006566.4		c.680G>A	p.Ser227Asn	missense	Exon 4 of 7	NP_006557.2	Q15762
CD226	NM_001303619.2		c.215G>A	p.Ser72Asn	missense	Exon 2 of 5	NP_001290548.1	J3QR77

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD226	ENST00000582621.6	TSL:1 MANE Select	c.680G>A	p.Ser227Asn	missense	Exon 3 of 6	ENSP00000461947.1	Q15762
CD226	ENST00000280200.8	TSL:1	c.680G>A	p.Ser227Asn	missense	Exon 4 of 7	ENSP00000280200.4	Q15762
CD226	ENST00000581982.5	TSL:1	c.215G>A	p.Ser72Asn	missense	Exon 2 of 5	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.9

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.076

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.35

M_CAP

Benign

0.0053

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.40

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.32

REVEL

Benign

0.019

Sift

Benign

0.47

Sift4G

Uncertain

0.057

Polyphen

0.24

Vest4

0.37

MutPred

0.35

Loss of disorder (P = 0.17)

MVP

0.47

MPC

0.40

ClinPred

0.095

GERP RS

-0.32

Varity_R

0.36

gMVP

0.39

Mutation Taster

=84/16

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over