rs686394

Positions:

• chr12-9922476-T-C

Variant summary

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

The NM_001130711.2(CLEC2A):​c.140-244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,220 control chromosomes in the GnomAD database, including 1,078 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 0.11 (1078 hom., cov: 32)
• Consequence: CLEC2A NM_001130711.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

Genes affected

CLEC2A (HGNC:24191): (C-type lectin domain family 2 member A) Enables protein homodimerization activity. Predicted to be involved in natural killer cell mediated cytotoxicity. Predicted to act upstream of or within several processes, including T cell receptor signaling pathway; regulation of actin filament polymerization; and regulation of interleukin-2 production. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC2A	NM_001130711.2	c.140-244A>G		intron_variant		ENST00000455827.2	NP_001124183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC2A	ENST00000455827.2	c.140-244A>G		intron_variant		1	NM_001130711.2	ENSP00000396163	P1
CLEC2A	ENST00000339766.8	c.140-244A>G		intron_variant		1		ENSP00000339732

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16014 AN: 152106 Hom.: 1074 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.105 AC: 16026 AN: 152220 Hom.: 1078 Cov.: 32 AF XY: 0.110 AC XY: 8205 AN XY: 74440

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.0729

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0833 Hom.: 928

Bravo AF: 0.101

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.80

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: rs686394; hg19: chr12-10075075;