rs75418532

Positions:

• chr18-69947331-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.46+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,446,224 control chromosomes in the GnomAD database, including 261 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 0.024 (144 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (117 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.46+30A>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.46+30A>G		intron_variant		1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3675 AN: 152114 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.00719 AC: 1531 AN: 212836 Hom.: 57 AF XY: 0.00525 AC XY: 609 AN XY: 115940

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.00304

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000129

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.00690

GnomAD4 exome AF: 0.00260 AC: 3366 AN: 1293992 Hom.: 117 Cov.: 18 AF XY: 0.00238 AC XY: 1552 AN XY: 650828

Gnomad4 AFR exome AF: 0.0841

Gnomad4 AMR exome AF: 0.00650

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000172

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000365

Gnomad4 OTH exome AF: 0.00577

GnomAD4 genome AF: 0.0243 AC: 3693 AN: 152232 Hom.: 144 Cov.: 32 AF XY: 0.0231 AC XY: 1723 AN XY: 74442

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0144 Hom.: 11

Bravo AF: 0.0276

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs75418532; hg19: chr18-67614567;