chr20-51538585-A-G

Variant names:

• chr20-51538585-A-G
• rs6021275
• NM_012340.5:c.130+3785T>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.130+3785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,030 control chromosomes in the GnomAD database, including 14,223 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 0.43 (14223 hom., cov: 32)
• Consequence: NFATC2 NM_173091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	NM_012340.5	MANE Select	c.130+3785T>C		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.130+3785T>C		intron	N/A	NP_775114.1
	NFATC2	NM_001258292.2		c.71-14475T>C		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.130+3785T>C		intron	N/A	ENSP00000360619.3
	NFATC2	ENST00000396009.7	TSL:1	c.130+3785T>C		intron	N/A	ENSP00000379330.3
	NFATC2	ENST00000609943.5	TSL:1	c.71-14475T>C		intron	N/A	ENSP00000477370.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65368 AN: 151912 Hom.: 14208 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.430 AC: 65420 AN: 152030 Hom.: 14223 Cov.: 32 AF XY: 0.423 AC XY: 31410 AN XY: 74308

African (AFR) AF: 0.441 AC: 18267 AN: 41442

American (AMR) AF: 0.374 AC: 5722 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1049 AN: 5172

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4818

European-Finnish (FIN) AF: 0.419 AC: 4434 AN: 10572

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31575 AN: 67962

Other (OTH) AF: 0.431 AC: 909 AN: 2110

Alfa AF: 0.448 Hom.: 45863

Bravo AF: 0.429

Asia WGS AF: 0.258 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		0.084
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: rs6021275; hg19: chr20-50155124;