Variant 20-51432351-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_012340.5(NFATC2):c.2438A>G(p.Tyr813Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NFATC2
NM_012340.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

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:

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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=0.21882662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5 linkuse as main transcript	c.2438A>G	p.Tyr813Cys	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.2438A>G	p.Tyr813Cys	missense_variant	9/11	1	NM_012340.5	A1	Q13469-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249868

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Aug 02, 2022

The c.2438A>G (p.Y813C) alteration is located in exon 9 (coding exon 9) of the NFATC2 gene. This alteration results from a A to G substitution at nucleotide position 2438, causing the tyrosine (Y) at amino acid position 813 to be replaced by a cysteine (C). 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

0.070

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

.;T;.;.;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.051

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D;.;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

N;N;.;.;N;.

REVEL

Benign

0.056

Sift

Benign

0.19

T;T;.;.;T;.

Sift4G

Benign

0.17

T;T;T;T;T;T

Polyphen

0.036

.;B;.;.;.;.

Vest4

0.51

MutPred

0.29

Loss of glycosylation at S814 (P = 0.1294);Loss of glycosylation at S814 (P = 0.1294);.;.;.;.;

MVP

0.068

MPC

0.48

ClinPred

0.22

GERP RS

5.5

Varity_R

0.10

gMVP

0.51

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