Variant 12-9913680-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001130711.2(CLEC2A):c.411G>A(p.Trp137Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,538,826 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

CLEC2A
NM_001130711.2 stop_gained, splice_region

Scores

Splicing: ADA: 0.03183

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-9913680-C-T is Benign according to our data. Variant chr12-9913680-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642698.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC2A	NM_001130711.2 linkuse as main transcript	c.411G>A	p.Trp137Ter	stop_gained, splice_region_variant	5/5	ENST00000455827.2	NP_001124183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC2A	ENST00000455827.2 linkuse as main transcript	c.411G>A	p.Trp137Ter	stop_gained, splice_region_variant	5/5	1	NM_001130711.2	ENSP00000396163	P1	Q6UVW9-1
CLEC2A	ENST00000339766.8 linkuse as main transcript	c.410+3020G>A		intron_variant		1		ENSP00000339732		Q6UVW9-2

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00927

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.000118

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000715

AC:

104

AN:

145458

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

77434

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000517

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.000323

AC:

448

AN:

1386586

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

205

AN XY:

684278

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000746

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000466

Gnomad4 OTH exome

AF:

0.000711

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152240

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00927

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000386

Hom.:

Bravo

AF:

0.00308

ESP6500AA

AF:

0.0108

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00167

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CLEC2A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Benign

0.43

M_CAP

Benign

0.0028

MutationTaster

Benign

1.0

D;D

Vest4

0.14

GERP RS

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.032

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.18

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