rs17208112

Variant names:

• chr18-69890193-G-A
• rs17208112
• NM_001303618.2:c.727+5508C>T

Variant summary

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

The NM_001303618.2(CD226):​c.727+5508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,154 control chromosomes in the GnomAD database, including 3,736 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 0.20 (3736 hom., cov: 32)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2	c.727+5508C>T		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.727+5508C>T		intron_variant	Intron 3 of 5	1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30684 AN: 152036 Hom.: 3735 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.202 AC: 30696 AN: 152154 Hom.: 3736 Cov.: 32 AF XY: 0.195 AC XY: 14521 AN XY: 74398

African (AFR) AF: 0.118 AC: 4881 AN: 41512

American (AMR) AF: 0.157 AC: 2404 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 993 AN: 3464

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5186

South Asian (SAS) AF: 0.220 AC: 1057 AN: 4812

European-Finnish (FIN) AF: 0.167 AC: 1767 AN: 10594

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18662 AN: 67980

Other (OTH) AF: 0.247 AC: 523 AN: 2114

Alfa AF: 0.265 Hom.: 8172

Bravo AF: 0.198

Asia WGS AF: 0.127 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.50
DANN	Benign	0.73
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17208112; hg19: chr18-67557429;