rs763362

Variant names:

• chr18-69864561-A-G
• rs763362
• NM_001303618.2:c.886-122T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-69864561-A-G
• chr18-69864561-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.886-122T>C		intron	N/A	NP_001290547.1
	CD226	NM_006566.4		c.886-122T>C		intron	N/A	NP_006557.2
	CD226	NM_001303619.2		c.421-122T>C		intron	N/A	NP_001290548.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.886-122T>C		intron	N/A	ENSP00000461947.1
	CD226	ENST00000280200.8	TSL:1	c.886-122T>C		intron	N/A	ENSP00000280200.4
	CD226	ENST00000581982.5	TSL:1	c.421-122T>C		intron	N/A	ENSP00000464084.1

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

African (AFR) AF: 0.368 AC: 6774 AN: 18430

American (AMR) AF: 0.350 AC: 8942 AN: 25580

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 6513 AN: 16040

East Asian (EAS) AF: 0.258 AC: 8861 AN: 34290

South Asian (SAS) AF: 0.426 AC: 23331 AN: 54804

European-Finnish (FIN) AF: 0.320 AC: 11567 AN: 36178

Middle Eastern (MID) AF: 0.522 AC: 2188 AN: 4188

European-Non Finnish (NFE) AF: 0.414 AC: 225159 AN: 543786

Other (OTH) AF: 0.397 AC: 14616 AN: 36812

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

African (AFR) AF: 0.355 AC: 14744 AN: 41504

American (AMR) AF: 0.349 AC: 5339 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1254 AN: 5176

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3114 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27158 AN: 67950

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.366 Hom.: 1292

Bravo AF: 0.377

Asia WGS AF: 0.320 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.79
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: rs763362; hg19: chr18-67531797; COSMIC: COSV54615429;