18-69864406-T-G

Position:

• chr18-69864406-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303618.2(CD226):​c.919A>C​(p.Ser307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. S307G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD226 NM_001303618.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06851444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.919A>C	p.Ser307Arg	missense_variant	6/6	ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.919A>C	p.Ser307Arg	missense_variant	6/6	1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.3
DANN	Benign	0.45
DEOGEN2	Benign	0.066	T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.15	N;.;.;.
REVEL	Benign	0.013
Sift	Benign	0.29	T;.;.;.
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.010	B;.;.;B
Vest4		0.15
MutPred		0.20		Gain of catalytic residue at S307 (P = 0.0067);.;.;Gain of catalytic residue at S307 (P = 0.0067);
MVP		0.40
MPC		0.21
ClinPred		0.031	T
GERP RS		0.23
Varity_R		0.049
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs763361; hg19: chr18-67531642;