20-51443611-T-C

Variant names:

• chr20-51443611-T-C
• rs228832
• NM_012340.5:c.1850-7850A>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.1850-7850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,008 control chromosomes in the GnomAD database, including 33,045 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 0.64 (33045 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 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.1850-7850A>G		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.1850-7850A>G		intron	N/A	NP_775114.1	Q13469-1
	NFATC2	NM_001258292.2		c.1790-7850A>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.1850-7850A>G		intron	N/A	ENSP00000360619.3	Q13469-2
	NFATC2	ENST00000396009.7	TSL:1	c.1850-7850A>G		intron	N/A	ENSP00000379330.3	Q13469-1
	NFATC2	ENST00000609943.5	TSL:1	c.1790-7850A>G		intron	N/A	ENSP00000477370.1	Q13469-4

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97220 AN: 151890 Hom.: 33039 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.640 AC: 97250 AN: 152008 Hom.: 33045 Cov.: 32 AF XY: 0.640 AC XY: 47581 AN XY: 74326

African (AFR) AF: 0.394 AC: 16324 AN: 41422

American (AMR) AF: 0.722 AC: 11027 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2878 AN: 5150

South Asian (SAS) AF: 0.713 AC: 3431 AN: 4814

European-Finnish (FIN) AF: 0.755 AC: 7992 AN: 10590

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50908 AN: 67974

Other (OTH) AF: 0.662 AC: 1399 AN: 2112

Alfa AF: 0.716 Hom.: 45872

Bravo AF: 0.627

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		0.014
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: rs228832; hg19: chr20-50060148;