18-69904374-C-G

Position:

• chr18-69904374-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303618.2(CD226):​c.383-8329G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,204 control chromosomes in the GnomAD database, including 60,725 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 0.89 (60725 hom., cov: 31)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.383-8329G>C		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.383-8329G>C		intron_variant		1	NM_001303618.2	ENSP00000461947	P1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134808 AN: 152086 Hom.: 60707 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.886 AC: 134876 AN: 152204 Hom.: 60725 Cov.: 31 AF XY: 0.889 AC XY: 66156 AN XY: 74426

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.911

Alfa AF: 0.889 Hom.: 2238

Bravo AF: 0.880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.68

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: rs4891786; hg19: chr18-67571610;