18-69883350-T-C

Variant names:

• chr18-69883350-T-C
• rs2051322
• NM_001303618.2:c.728-10104A>G

Variant summary

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

The NM_001303618.2(CD226):​c.728-10104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,098 control chromosomes in the GnomAD database, including 46,586 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 0.77 (46586 hom., cov: 32)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2	c.728-10104A>G		intron_variant	Intron 3 of 5	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.728-10104A>G		intron_variant	Intron 3 of 5	1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116987 AN: 151984 Hom.: 46586 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.769 AC: 117019 AN: 152098 Hom.: 46586 Cov.: 32 AF XY: 0.770 AC XY: 57263 AN XY: 74366

African (AFR) AF: 0.546 AC: 22620 AN: 41426

American (AMR) AF: 0.770 AC: 11774 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3031 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3894 AN: 5160

South Asian (SAS) AF: 0.789 AC: 3802 AN: 4820

European-Finnish (FIN) AF: 0.885 AC: 9387 AN: 10608

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59907 AN: 68012

Other (OTH) AF: 0.793 AC: 1674 AN: 2112

Alfa AF: 0.845 Hom.: 30119

Bravo AF: 0.749

Asia WGS AF: 0.767 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.25
PhyloP100		-0.90
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: rs2051322; hg19: chr18-67550586;