chr20-51391469-A-AG

Position:

• chr20-51391469-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012340.5(NFATC2):​c.*45-19_*45-18insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,064,702 control chromosomes in the GnomAD database, including 37,054 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (14480 hom., cov: 0)
  • Exomes 𝑓: 0.32 (22574 hom.)
• Consequence: NFATC2 NM_012340.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0180

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]

LOC105372663 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-51391469-A-AG is Benign according to our data. Variant chr20-51391469-A-AG is described in ClinVar as [Benign]. Clinvar id is 2975968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC2	NM_012340.5	c.*45-19_*45-18insC		intron_variant		ENST00000371564.8
LOC105372663	XR_936848.3	n.483-5259dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC2	ENST00000371564.8	c.*45-19_*45-18insC		intron_variant		1	NM_012340.5	A1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 63893 AN: 140292 Hom.: 14455 Cov.: 0

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.387

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.321 AC: 296713 AN: 924336 Hom.: 22574 Cov.: 31 AF XY: 0.321 AC XY: 151764 AN XY: 472804

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.456 AC: 63950 AN: 140366 Hom.: 14480 Cov.: 0 AF XY: 0.450 AC XY: 30514 AN XY: 67806

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3830840; hg19: chr20-50008006;