rs17842596

Positions:

• chr18-69898343-G-A
• chr18-69898343-G-C

Variant summary

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

The NM_001303618.2(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_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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 = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.383-2298C>T		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.383-2298C>T		intron_variant		1	NM_001303618.2	ENSP00000461947.1

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

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.522

Alfa AF: 0.588 Hom.: 35207

Bravo AF: 0.533

Asia WGS AF: 0.620 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.71

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: rs17842596; hg19: chr18-67565579;