Variant 12-9913668-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130711.2(CLEC2A):c.423A>G(p.Ile141Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

CLEC2A
NM_001130711.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.65

Variant links:

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]

CLEC2A links:

CLEC2A (HGNC:):

CLEC2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08443481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC2A	NM_001130711.2 linkuse as main transcript	c.423A>G	p.Ile141Met	missense_variant	5/5	ENST00000455827.2	NP_001124183.1	Q6UVW9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC2A	ENST00000455827.2 linkuse as main transcript	c.423A>G	p.Ile141Met	missense_variant	5/5	1	NM_001130711.2	ENSP00000396163.1		Q6UVW9-1
CLEC2A	ENST00000339766.8 linkuse as main transcript	c.410+3032A>G		intron_variant		1		ENSP00000339732.4		Q6UVW9-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.423A>G (p.I141M) alteration is located in exon 5 (coding exon 5) of the CLEC2A gene. This alteration results from a A to G substitution at nucleotide position 423, causing the isoleucine (I) at amino acid position 141 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.62

DANN

Benign

0.95

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.27

M_CAP

Benign

0.00092

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.33

PROVEAN

Benign

1.1

REVEL

Benign

0.029

Sift

Benign

0.050

Sift4G

Uncertain

0.060

Polyphen

0.68

Vest4

0.12

MutPred

0.44

Gain of catalytic residue at F146 (P = 2e-04);

MVP

0.20

ClinPred

0.17

GERP RS

-3.1

Varity_R

0.13

gMVP

0.053

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over