chr18-69864561-A-G

Position:

• chr18-69864561-A-G

Variant summary

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

The NM_001303618.2(CD226):​c.886-122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 922,208 control chromosomes in the GnomAD database, including 73,085 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 0.37 (10624 hom., cov: 32)
  • Exomes 𝑓: 0.40 (62461 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.886-122T>C		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.886-122T>C		intron_variant		1	NM_001303618.2	ENSP00000461947	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56255 AN: 151982 Hom.: 10610 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.400 AC: 307951 AN: 770108 Hom.: 62461 AF XY: 0.402 AC XY: 159372 AN XY: 396058

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.370 AC: 56310 AN: 152100 Hom.: 10624 Cov.: 32 AF XY: 0.364 AC XY: 27090 AN XY: 74360

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.403

Alfa AF: 0.366 Hom.: 1250

Bravo AF: 0.377

Asia WGS AF: 0.320 AC: 1119 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	12
DANN	Benign	0.79

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: rs763362; hg19: chr18-67531797; COSMIC: COSV54615429;