rs2469434

Positions:

• chr18-69876810-T-C

Variant summary

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

The NM_001303618.2(CD226):​c.728-3564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 150,224 control chromosomes in the GnomAD database, including 14,742 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 0.44 (14742 hom., cov: 28)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.728-3564A>G		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.728-3564A>G		intron_variant		1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 65396 AN: 150126 Hom.: 14717 Cov.: 28

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.436 AC: 65474 AN: 150224 Hom.: 14742 Cov.: 28 AF XY: 0.431 AC XY: 31603 AN XY: 73252

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.452

Alfa AF: 0.418 Hom.: 1673

Bravo AF: 0.448

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.63

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: rs2469434; hg19: chr18-67544046;