chr20-51417155-G-T

Variant names:

• chr20-51417155-G-T
• rs768538
• NM_012340.5:c.2722+14912C>A

Variant summary

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

The NM_012340.5(NFATC2):​c.2722+14912C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,962 control chromosomes in the GnomAD database, including 26,130 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 0.55 (26130 hom., cov: 31)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	NM_012340.5	MANE Select	c.2722+14912C>A		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.2722+14912C>A		intron	N/A	NP_775114.1
	NFATC2	NM_001258292.2		c.2662+14912C>A		intron	N/A	NP_001245221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	ENST00000371564.8	TSL:1 MANE Select	c.2722+14912C>A		intron	N/A	ENSP00000360619.3
	NFATC2	ENST00000396009.7	TSL:1	c.2722+14912C>A		intron	N/A	ENSP00000379330.3
	NFATC2	ENST00000609943.5	TSL:1	c.2662+14912C>A		intron	N/A	ENSP00000477370.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82973 AN: 151844 Hom.: 26140 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.546 AC: 82949 AN: 151962 Hom.: 26130 Cov.: 31 AF XY: 0.544 AC XY: 40446 AN XY: 74282

African (AFR) AF: 0.222 AC: 9211 AN: 41434

American (AMR) AF: 0.553 AC: 8444 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1721 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2351 AN: 5158

South Asian (SAS) AF: 0.637 AC: 3072 AN: 4820

European-Finnish (FIN) AF: 0.702 AC: 7410 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48643 AN: 67936

Other (OTH) AF: 0.566 AC: 1193 AN: 2106

Alfa AF: 0.649 Hom.: 29521

Bravo AF: 0.522

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		0.018
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: rs768538; hg19: chr20-50033692;