20-51432542-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

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]

ACMG classification

Verdict is Benign. Variant got -11 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.41 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.2247C>T	p.Ala749=	synonymous_variant	9/11	1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152178 Hom.: 2 Cov.: 32

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.: 4 AF XY: 0.00283 AC XY: 291 AN XY: 102888

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.: 19 Cov.: 31 AF XY: 0.00211 AC XY: 1454 AN XY: 688426

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.: 2 Cov.: 32 AF XY: 0.00188 AC XY: 140 AN XY: 74456

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.: 3

Bravo AF: 0.00124

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs145906106; hg19: chr20-50049079; COSMIC: COSV65355078;