18-69898343-G-A

Variant names:

• chr18-69898343-G-A
• rs17842596
• NM_001303618.2:c.383-2298C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006566.4(CD226):​c.383-2298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,934 control chromosomes in the GnomAD database, including 23,679 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 0.55 (23679 hom., cov: 31)
• Consequence: CD226 NM_006566.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 6 publications found

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]

ENSG00000304227 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.383-2298C>T		intron	N/A	NP_001290547.1
	CD226	NM_006566.4		c.383-2298C>T		intron	N/A	NP_006557.2
	CD226	NM_001303619.2		c.-83-2298C>T		intron	N/A	NP_001290548.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.383-2298C>T		intron	N/A	ENSP00000461947.1
	CD226	ENST00000280200.8	TSL:1	c.383-2298C>T		intron	N/A	ENSP00000280200.4
	CD226	ENST00000581982.5	TSL:1	c.-83-2298C>T		intron	N/A	ENSP00000464084.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82855 AN: 151818 Hom.: 23687 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.545 AC: 82871 AN: 151934 Hom.: 23679 Cov.: 31 AF XY: 0.552 AC XY: 40986 AN XY: 74240

African (AFR) AF: 0.372 AC: 15413 AN: 41412

American (AMR) AF: 0.599 AC: 9147 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2094 AN: 3466

East Asian (EAS) AF: 0.687 AC: 3530 AN: 5136

South Asian (SAS) AF: 0.581 AC: 2794 AN: 4806

European-Finnish (FIN) AF: 0.669 AC: 7056 AN: 10554

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41109 AN: 67958

Other (OTH) AF: 0.522 AC: 1104 AN: 2114

Alfa AF: 0.582 Hom.: 43707

Bravo AF: 0.533

Asia WGS AF: 0.620 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.71
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17842596; hg19: chr18-67565579;