chr18-69863790-C-A

Position:

• chr18-69863790-C-A

Variant summary

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

The NM_001303618.2(CD226):​c.*524G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,456 control chromosomes in the GnomAD database, including 10,044 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 0.36 (9992 hom., cov: 32)
  • Exomes 𝑓: 0.42 (52 hom.)
• Consequence: CD226 NM_001303618.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.*524G>T		3_prime_UTR_variant	6/6	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.*524G>T		3_prime_UTR_variant	6/6	1	NM_001303618.2	ENSP00000461947.1
CD226	ENST00000280200.8	c.*524G>T		3_prime_UTR_variant	7/7	1		ENSP00000280200.4
CD226	ENST00000581982.5	c.*524G>T		3_prime_UTR_variant	5/5	1		ENSP00000464084.1
CD226	ENST00000578928.1	n.110-21395G>T		intron_variant		4		ENSP00000463152.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54276 AN: 151890 Hom.: 9981 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.424 AC: 190 AN: 448 Hom.: 52 Cov.: 0 AF XY: 0.443 AC XY: 108 AN XY: 244

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.357 AC: 54324 AN: 152008 Hom.: 9992 Cov.: 32 AF XY: 0.352 AC XY: 26164 AN XY: 74272

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.391

Alfa AF: 0.375 Hom.: 2348

Bravo AF: 0.362

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.36

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: rs34794968; hg19: chr18-67531026;