NM_012340.5:c.1333-90A>G

Variant names:

• chr20-51475750-T-C
• rs6021231
• NM_012340.5:c.1333-90A>G

Variant summary

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

The NM_012340.5(NFATC2):​c.1333-90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,243,730 control chromosomes in the GnomAD database, including 142,667 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 0.51 (20664 hom., cov: 30)
  • Exomes 𝑓: 0.47 (122003 hom.)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012340.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	NM_012340.5	MANE Select	c.1333-90A>G		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.1333-90A>G		intron	N/A	NP_775114.1	Q13469-1
	NFATC2	NM_001258292.2		c.1273-90A>G		intron	N/A	NP_001245221.1	Q13469-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	ENST00000371564.8	TSL:1 MANE Select	c.1333-90A>G		intron	N/A	ENSP00000360619.3	Q13469-2
	NFATC2	ENST00000396009.7	TSL:1	c.1333-90A>G		intron	N/A	ENSP00000379330.3	Q13469-1
	NFATC2	ENST00000609943.5	TSL:1	c.1273-90A>G		intron	N/A	ENSP00000477370.1	Q13469-4

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77528 AN: 151798 Hom.: 20611 Cov.: 30

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.470 AC: 512626 AN: 1091814 Hom.: 122003 AF XY: 0.468 AC XY: 256422 AN XY: 547422

African (AFR) AF: 0.671 AC: 16676 AN: 24842

American (AMR) AF: 0.525 AC: 16316 AN: 31106

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 12057 AN: 21352

East Asian (EAS) AF: 0.418 AC: 14374 AN: 34356

South Asian (SAS) AF: 0.437 AC: 29949 AN: 68530

European-Finnish (FIN) AF: 0.328 AC: 15328 AN: 46796

Middle Eastern (MID) AF: 0.566 AC: 2215 AN: 3916

European-Non Finnish (NFE) AF: 0.470 AC: 382576 AN: 813626

Other (OTH) AF: 0.489 AC: 23135 AN: 47290

GnomAD4 genome AF: 0.511 AC: 77625 AN: 151916 Hom.: 20664 Cov.: 30 AF XY: 0.503 AC XY: 37353 AN XY: 74236

African (AFR) AF: 0.661 AC: 27382 AN: 41408

American (AMR) AF: 0.496 AC: 7574 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1955 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2102 AN: 5156

South Asian (SAS) AF: 0.429 AC: 2062 AN: 4806

European-Finnish (FIN) AF: 0.336 AC: 3541 AN: 10546

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31444 AN: 67952

Other (OTH) AF: 0.514 AC: 1086 AN: 2114

Alfa AF: 0.486 Hom.: 56748

Bravo AF: 0.532

Asia WGS AF: 0.444 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.37
PhyloP100		-0.66
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: rs6021231; hg19: chr20-50092287; COSMIC: COSV65356629;