chr18-69895812-C-T

Variant names:

• chr18-69895812-C-T
• rs148019790
• NM_001303618.2:c.616G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001303618.2(CD226):​c.616G>A​(p.Val206Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: CD226 NM_001303618.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.329
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024668366).

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.616G>A	p.Val206Ile	missense	Exon 3 of 6	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.616G>A	p.Val206Ile	missense	Exon 4 of 7	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.151G>A	p.Val51Ile	missense	Exon 2 of 5	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.616G>A	p.Val206Ile	missense	Exon 3 of 6	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.616G>A	p.Val206Ile	missense	Exon 4 of 7	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.151G>A	p.Val51Ile	missense	Exon 2 of 5	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251488 AF XY: 0.000118

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000200 AC: 293 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.000208 AC XY: 151 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000243 AC: 270 AN: 1111988

Other (OTH) AF: 0.000149 AC: 9 AN: 60396

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74336

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.000181

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.16
DANN	Benign	0.64
DEOGEN2	Benign	0.076	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.33
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.014
Sift	Benign	0.64	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.062
MVP		0.27
MPC		0.15
ClinPred		0.011	T
GERP RS		-3.5
Varity_R		0.14
gMVP		0.53
Mutation Taster		=92/8	polymorphism

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: rs148019790; hg19: chr18-67563048; COSMIC: COSV99711511; COSMIC: COSV99711511;