20-51451765-C-G

Variant names:

• chr20-51451765-C-G
• rs228837
• NM_012340.5:c.1849+2783G>C

Variant summary

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

The NM_173091.4(NFATC2):​c.1849+2783G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,024 control chromosomes in the GnomAD database, including 36,129 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 0.69 (36129 hom., cov: 31)
• Consequence: NFATC2 NM_173091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173091.4. 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.1849+2783G>C		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.1849+2783G>C		intron	N/A	NP_775114.1
	NFATC2	NM_001258292.2		c.1789+2783G>C		intron	N/A	NP_001245221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	ENST00000371564.8	TSL:1 MANE Select	c.1849+2783G>C		intron	N/A	ENSP00000360619.3
	NFATC2	ENST00000396009.7	TSL:1	c.1849+2783G>C		intron	N/A	ENSP00000379330.3
	NFATC2	ENST00000609943.5	TSL:1	c.1789+2783G>C		intron	N/A	ENSP00000477370.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104043 AN: 151906 Hom.: 36088 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.685 AC: 104138 AN: 152024 Hom.: 36129 Cov.: 31 AF XY: 0.693 AC XY: 51525 AN XY: 74300

African (AFR) AF: 0.745 AC: 30895 AN: 41472

American (AMR) AF: 0.656 AC: 10023 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2038 AN: 3466

East Asian (EAS) AF: 0.937 AC: 4832 AN: 5156

South Asian (SAS) AF: 0.774 AC: 3729 AN: 4816

European-Finnish (FIN) AF: 0.753 AC: 7963 AN: 10578

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42459 AN: 67948

Other (OTH) AF: 0.657 AC: 1383 AN: 2106

Alfa AF: 0.549 Hom.: 1757

Bravo AF: 0.679

Asia WGS AF: 0.872 AC: 3030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.077
DANN	Benign	0.46
PhyloP100		-1.6
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: rs228837; hg19: chr20-50068302;