chr20-51401774-G-A

Variant names:

• chr20-51401774-G-A
• rs4811172
• NM_012340.5:c.2723-3044C>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.2723-3044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,234 control chromosomes in the GnomAD database, including 63,747 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 0.91 (63747 hom., cov: 32)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 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.2723-3044C>T		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.2723-10323C>T		intron	N/A	NP_775114.1	Q13469-1
	NFATC2	NM_001258292.2		c.2663-10323C>T		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.2723-3044C>T		intron	N/A	ENSP00000360619.3	Q13469-2
	NFATC2	ENST00000396009.7	TSL:1	c.2723-10323C>T		intron	N/A	ENSP00000379330.3	Q13469-1
	NFATC2	ENST00000609943.5	TSL:1	c.2663-10323C>T		intron	N/A	ENSP00000477370.1	Q13469-4

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139161 AN: 152116 Hom.: 63703 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.915 AC: 139262 AN: 152234 Hom.: 63747 Cov.: 32 AF XY: 0.913 AC XY: 67974 AN XY: 74428

African (AFR) AF: 0.932 AC: 38699 AN: 41528

American (AMR) AF: 0.919 AC: 14048 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4932 AN: 5186

South Asian (SAS) AF: 0.944 AC: 4552 AN: 4824

European-Finnish (FIN) AF: 0.916 AC: 9699 AN: 10594

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61603 AN: 68022

Other (OTH) AF: 0.905 AC: 1908 AN: 2108

Alfa AF: 0.904 Hom.: 22539

Bravo AF: 0.917

Asia WGS AF: 0.953 AC: 3313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.043
DANN	Benign	0.20
PhyloP100		-1.5
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: rs4811172; hg19: chr20-50018311;