rs686394

Variant names:

• chr12-9922476-T-C
• rs686394
• NM_001130711.2:c.140-244A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130711.2. 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
	CLEC2A	NM_001130711.2	MANE Select	c.140-244A>G		intron	N/A	NP_001124183.1
	CLEC2A	NM_207375.3		c.140-244A>G		intron	N/A	NP_997258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2A	ENST00000455827.2	TSL:1 MANE Select	c.140-244A>G		intron	N/A	ENSP00000396163.1
	CLEC2A	ENST00000339766.8	TSL:1	c.140-244A>G		intron	N/A	ENSP00000339732.4

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

African (AFR) AF: 0.141 AC: 5854 AN: 41532

American (AMR) AF: 0.104 AC: 1595 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3468

East Asian (EAS) AF: 0.169 AC: 877 AN: 5182

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4820

European-Finnish (FIN) AF: 0.0729 AC: 773 AN: 10606

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0668 AC: 4546 AN: 68012

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.0854 Hom.: 1299

Bravo AF: 0.101

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.80
PhyloP100		0.31
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: rs686394; hg19: chr12-10075075;