rs880324

Variant names:

• chr20-51437653-G-A
• rs880324
• NM_012340.5:c.1850-1892C>T

Variant summary

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

The NM_012340.5(NFATC2):​c.1850-1892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,834 control chromosomes in the GnomAD database, including 3,789 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 0.22 (3789 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 11 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

ENSG00000300496 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.1850-1892C>T		intron_variant	Intron 6 of 10	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.1850-1892C>T		intron_variant	Intron 6 of 10	1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33130 AN: 151714 Hom.: 3791 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.218 AC: 33147 AN: 151834 Hom.: 3789 Cov.: 32 AF XY: 0.211 AC XY: 15638 AN XY: 74222

African (AFR) AF: 0.258 AC: 10694 AN: 41386

American (AMR) AF: 0.228 AC: 3479 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3466

East Asian (EAS) AF: 0.0192 AC: 99 AN: 5166

South Asian (SAS) AF: 0.150 AC: 721 AN: 4798

European-Finnish (FIN) AF: 0.149 AC: 1566 AN: 10510

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14982 AN: 67946

Other (OTH) AF: 0.222 AC: 468 AN: 2104

Alfa AF: 0.222 Hom.: 8461

Bravo AF: 0.229

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.65
PhyloP100		-0.0040
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: rs880324; hg19: chr20-50054190;