18-69867472-G-A

Position:

• chr18-69867472-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001303618.2(CD226):​c.831-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,088,650 control chromosomes in the GnomAD database, including 511 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 0.027 (68 hom., cov: 32)
  • Exomes 𝑓: 0.028 (443 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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=-0.97).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0267 (4053/152056) while in subpopulation NFE AF= 0.0307 (2086/67996). AF 95% confidence interval is 0.0296. There are 68 homozygotes in gnomad4. There are 1938 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.831-61C>T		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.831-61C>T		intron_variant		1	NM_001303618.2	ENSP00000461947	P1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4043 AN: 151938 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.0276 AC: 25858 AN: 936594 Hom.: 443 AF XY: 0.0276 AC XY: 13490 AN XY: 489294

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00939

Gnomad4 EAS exome AF: 0.00401

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0269

GnomAD4 genome AF: 0.0267 AC: 4053 AN: 152056 Hom.: 68 Cov.: 32 AF XY: 0.0261 AC XY: 1938 AN XY: 74336

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0272 Hom.: 6

Bravo AF: 0.0255

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.39

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: rs62090790; hg19: chr18-67534708; COSMIC: COSV54615440;