20-51543496-G-T

Variant names:

• chr20-51543496-G-T
• rs4811191
• ENST00000609943.5:c.70+19064C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001258292.2(NFATC2):​c.70+19064C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: NFATC2 NM_001258292.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 4 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

ENSG00000304242 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	NM_001258292.2		c.70+19064C>A		intron	N/A	NP_001245221.1	Q13469-4
	NFATC2	NM_001136021.3		c.70+19064C>A		intron	N/A	NP_001129493.1	Q13469-3
	NFATC2	NM_001258295.2		c.-14+19064C>A		intron	N/A	NP_001245224.1	B5B2P4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC2	ENST00000609943.5	TSL:1	c.70+19064C>A		intron	N/A	ENSP00000477370.1	Q13469-4
	NFATC2	ENST00000414705.5	TSL:1	c.70+19064C>A		intron	N/A	ENSP00000396471.1	Q13469-3
	NFATC2	ENST00000609507.1	TSL:1	c.-14+19064C>A		intron	N/A	ENSP00000477342.1	Q13469-5

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 977

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.45
PhyloP100		0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4811191; hg19: chr20-50160035;