rs17728960

Variant names:

• chr20-51513177-T-C
• rs17728960
• NM_012340.5:c.1332+3607A>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.1332+3607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 152,348 control chromosomes in the GnomAD database, including 255 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 0.051 (255 hom., cov: 33)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.999
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.1332+3607A>G		intron_variant	Intron 3 of 10	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.1332+3607A>G		intron_variant	Intron 3 of 10	1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7709 AN: 152230 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0507 AC: 7720 AN: 152348 Hom.: 255 Cov.: 33 AF XY: 0.0499 AC XY: 3717 AN XY: 74502

African (AFR) AF: 0.0299 AC: 1245 AN: 41582

American (AMR) AF: 0.0453 AC: 694 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3468

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5194

South Asian (SAS) AF: 0.0441 AC: 213 AN: 4828

European-Finnish (FIN) AF: 0.0577 AC: 613 AN: 10624

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4624 AN: 68026

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0542 Hom.: 33

Bravo AF: 0.0486

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		1.0
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: rs17728960; hg19: chr20-50129716;