18-69876810-T-C

Variant names:

• chr18-69876810-T-C
• rs2469434
• NM_001303618.2:c.728-3564A>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.728-3564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 150,224 control chromosomes in the GnomAD database, including 14,742 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 0.44 (14742 hom., cov: 28)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 34 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 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.728-3564A>G		intron	N/A	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.728-3564A>G		intron	N/A	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.263-3564A>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.728-3564A>G		intron	N/A	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.728-3564A>G		intron	N/A	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.263-3564A>G		intron	N/A	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes AF: 0.436 AC: 65396 AN: 150126 Hom.: 14717 Cov.: 28

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 65474 AN: 150224 Hom.: 14742 Cov.: 28 AF XY: 0.431 AC XY: 31603 AN XY: 73252

African (AFR) AF: 0.529 AC: 21476 AN: 40634

American (AMR) AF: 0.385 AC: 5820 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1616 AN: 3458

East Asian (EAS) AF: 0.340 AC: 1732 AN: 5096

South Asian (SAS) AF: 0.448 AC: 2138 AN: 4772

European-Finnish (FIN) AF: 0.323 AC: 3242 AN: 10036

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27807 AN: 67812

Other (OTH) AF: 0.452 AC: 942 AN: 2084

Alfa AF: 0.417 Hom.: 19680

Bravo AF: 0.448

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2469434; hg19: chr18-67544046;