chr20-51524725-T-C

Variant names:

• chr20-51524725-T-C
• rs6021270
• NM_012340.5:c.131-615A>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.131-615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 152,062 control chromosomes in the GnomAD database, including 270 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 0.057 (270 hom., cov: 31)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFATC2	NM_012340.5	c.131-615A>G		intron_variant	Intron 1 of 10	ENST00000371564.8	NP_036472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8	c.131-615A>G		intron_variant	Intron 1 of 10	1	NM_012340.5	ENSP00000360619.3

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8663 AN: 151944 Hom.: 271 Cov.: 31

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0570 AC: 8670 AN: 152062 Hom.: 270 Cov.: 31 AF XY: 0.0574 AC XY: 4263 AN XY: 74320

African (AFR) AF: 0.0525 AC: 2177 AN: 41492

American (AMR) AF: 0.0446 AC: 682 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3466

East Asian (EAS) AF: 0.0677 AC: 350 AN: 5168

South Asian (SAS) AF: 0.0661 AC: 318 AN: 4812

European-Finnish (FIN) AF: 0.0590 AC: 623 AN: 10552

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0616 AC: 4184 AN: 67974

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0602 Hom.: 390

Bravo AF: 0.0550

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.65
PhyloP100		-1.2
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: rs6021270; hg19: chr20-50141264;