rs12604328

Positions:

• chr18-69857737-T-C
• chr18-69857737-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000582621.6(CD226):​c.*6577A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,120 control chromosomes in the GnomAD database, including 4,153 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 0.22 (4153 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CD226 ENST00000582621.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.*6577A>G		3_prime_UTR_variant	6/6	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.*6577A>G		3_prime_UTR_variant	6/6	1	NM_001303618.2	ENSP00000461947	P1
CD226	ENST00000280200.8	c.*6577A>G		3_prime_UTR_variant	7/7	1		ENSP00000280200	P1
CD226	ENST00000578928.1	c.110-15342A>G		intron_variant, NMD_transcript_variant		4		ENSP00000463152

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34134 AN: 152002 Hom.: 4152 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.253

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.224 AC: 34144 AN: 152120 Hom.: 4153 Cov.: 33 AF XY: 0.225 AC XY: 16744 AN XY: 74350

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.250

Alfa AF: 0.260 Hom.: 7753

Bravo AF: 0.227

Asia WGS AF: 0.241 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.74

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: rs12604328; hg19: chr18-67524973;