18-69896073-A-C

Variant names:

• chr18-69896073-A-C
• rs1630425
• NM_001303618.2:c.383-28T>G

Variant summary

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

The NM_001303618.2(CD226):​c.383-28T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,588,294 control chromosomes in the GnomAD database, including 784,963 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 0.97 (71466 hom., cov: 32)
  • Exomes 𝑓: 1.0 (713497 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 6 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]

ENSG00000304227 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.383-28T>G		intron	N/A	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.383-28T>G		intron	N/A	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.-83-28T>G		intron	N/A	NP_001290548.1	J3QR77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.383-28T>G		intron	N/A	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.383-28T>G		intron	N/A	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.-83-28T>G		intron	N/A	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147193 AN: 152156 Hom.: 71407 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.978

GnomAD2 exomes AF: 0.991 AC: 229148 AN: 231268 AF XY: 0.993

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.994

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.997 AC: 1431274 AN: 1436020 Hom.: 713497 Cov.: 35 AF XY: 0.997 AC XY: 710525 AN XY: 712568

African (AFR) AF: 0.885 AC: 29314 AN: 33138

American (AMR) AF: 0.993 AC: 43660 AN: 43950

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25660 AN: 25660

East Asian (EAS) AF: 1.00 AC: 39444 AN: 39444

South Asian (SAS) AF: 1.00 AC: 84967 AN: 84986

European-Finnish (FIN) AF: 1.00 AC: 41281 AN: 41282

Middle Eastern (MID) AF: 0.995 AC: 5664 AN: 5694

European-Non Finnish (NFE) AF: 1.00 AC: 1102015 AN: 1102180

Other (OTH) AF: 0.993 AC: 59269 AN: 59686

GnomAD4 genome AF: 0.967 AC: 147312 AN: 152274 Hom.: 71466 Cov.: 32 AF XY: 0.969 AC XY: 72131 AN XY: 74450

African (AFR) AF: 0.886 AC: 36791 AN: 41520

American (AMR) AF: 0.989 AC: 15135 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.999 AC: 4827 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68014 AN: 68030

Other (OTH) AF: 0.978 AC: 2070 AN: 2116

Alfa AF: 0.989 Hom.: 86359

Bravo AF: 0.963

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.32
PhyloP100		-0.80
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: rs1630425; hg19: chr18-67563309;