Variant chr20-51432542-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012340.5(NFATC2):c.2247C>T(p.Ala749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,549,364 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 19 hom. )

Consequence

NFATC2
NM_012340.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.410

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 20-51432542-G-A is Benign according to our data. Variant chr20-51432542-G-A is described in ClinVar as [Benign]. Clinvar id is 790890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.41 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC2	NM_012340.5 linkuse as main transcript	c.2247C>T	p.Ala749=	synonymous_variant	9/11	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8 linkuse as main transcript	c.2247C>T	p.Ala749=	synonymous_variant	9/11	1	NM_012340.5	ENSP00000360619	A1	Q13469-2

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

227

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00239

AC:

462

AN:

192968

Hom.:

AF XY:

0.00283

AC XY:

291

AN XY:

102888

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00173

AC:

2410

AN:

1397068

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1454

AN XY:

688426

show subpopulations

Gnomad4 AFR exome

AF:

0.000223

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000822

Gnomad4 OTH exome

AF:

0.00284

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152296

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00124

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.3

DANN

Benign

0.68

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