20-51502303-C-T

Variant names:

• chr20-51502303-C-T
• rs6123045
• NM_012340.5:c.1332+14481G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012340.5(NFATC2):​c.1332+14481G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,090 control chromosomes in the GnomAD database, including 5,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5645 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• joint contractures, osteochondromas, and B-cell lymphoma

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.1332+14481G>A		intron_variant	Intron 3 of 10	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.1332+14481G>A		intron_variant	Intron 3 of 10	1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40431 AN: 151972 Hom.: 5653 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40417 AN: 152090 Hom.: 5645 Cov.: 32 AF XY: 0.268 AC XY: 19953 AN XY: 74334

African (AFR) AF: 0.183 AC: 7611 AN: 41526

American (AMR) AF: 0.264 AC: 4025 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3466

East Asian (EAS) AF: 0.395 AC: 2040 AN: 5162

South Asian (SAS) AF: 0.315 AC: 1516 AN: 4814

European-Finnish (FIN) AF: 0.280 AC: 2958 AN: 10572

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20189 AN: 67980

Other (OTH) AF: 0.290 AC: 610 AN: 2102

Alfa AF: 0.286 Hom.: 11001

Bravo AF: 0.257

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6123045; hg19: chr20-50118842;