rs2273642

Variant names:

• chr20-51516550-G-A
• rs2273642
• NM_012340.5:c.1332+234C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-51516550-G-A
• chr20-51516550-G-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.1332+234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,070 control chromosomes in the GnomAD database, including 5,745 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 0.27 (5745 hom., cov: 33)
• Consequence: NFATC2 NM_173091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 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.1332+234C>T		intron	N/A	NP_036472.2
	NFATC2	NM_173091.4		c.1332+234C>T		intron	N/A	NP_775114.1
	NFATC2	NM_001258292.2		c.1272+234C>T		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.1332+234C>T		intron	N/A	ENSP00000360619.3
	NFATC2	ENST00000396009.7	TSL:1	c.1332+234C>T		intron	N/A	ENSP00000379330.3
	NFATC2	ENST00000609943.5	TSL:1	c.1272+234C>T		intron	N/A	ENSP00000477370.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41066 AN: 151952 Hom.: 5738 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.270 AC: 41125 AN: 152070 Hom.: 5745 Cov.: 33 AF XY: 0.270 AC XY: 20040 AN XY: 74328

African (AFR) AF: 0.200 AC: 8290 AN: 41480

American (AMR) AF: 0.341 AC: 5212 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1446 AN: 5180

South Asian (SAS) AF: 0.276 AC: 1330 AN: 4814

European-Finnish (FIN) AF: 0.247 AC: 2612 AN: 10556

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20222 AN: 67984

Other (OTH) AF: 0.276 AC: 585 AN: 2116

Alfa AF: 0.291 Hom.: 7263

Bravo AF: 0.276

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.028
DANN	Benign	0.39
PhyloP100		-1.8
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: rs2273642; hg19: chr20-50133089;