Variant 20-51432246-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012340.5(NFATC2):c.2543C>T(p.Pro848Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000635 in 1,614,168 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 2 hom. )

Consequence

NFATC2
NM_012340.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

NFATC2 (HGNC:7776): (nuclear factor of activated T cells 2) This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Apr 2012]

NFATC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005271673).

BP6

Variant 20-51432246-G-A is Benign according to our data. Variant chr20-51432246-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781568.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5 linkuse as main transcript	c.2543C>T	p.Pro848Leu	missense_variant	9/11	ENST00000371564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8 linkuse as main transcript	c.2543C>T	p.Pro848Leu	missense_variant	9/11	1	NM_012340.5	A1	Q13469-2

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

320

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000206

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000723

AC:

181

AN:

250452

Hom.:

AF XY:

0.000524

AC XY:

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.00923

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000483

AC:

706

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

315

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00938

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00106

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00209

AC:

319

AN:

152308

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00720

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000449

Hom.:

Bravo

AF:

0.00271

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Invitae

Apr 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D;D;.;D;D

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0053

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;.;.;N;.

REVEL

Benign

0.068

Sift

Uncertain

0.0040

D;D;.;.;D;.

Sift4G

Benign

0.25

T;T;T;T;T;T

Polyphen

0.97

.;D;.;.;.;.

Vest4

0.22

MVP

0.21

MPC

0.61

ClinPred

0.034

GERP RS

4.5

Varity_R

0.052

gMVP

0.17

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