Genetic Variant NFATC2:c.*45-19dupC (chr20-51391469-A-AG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_012340.5(NFATC2):c.*45-19dupC 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0180

Variant links:

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 links:

LOC105372663 (HGNC:):

LOC105372663 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFATC2	NM_012340.5 link	c.*45-19dupC		intron_variant	Intron 10 of 10	ENST00000371564.8	NP_036472.2	Q13469-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFATC2	ENST00000371564.8 link	c.45-19_45-18insC		intron_variant	Intron 10 of 10	1	NM_012340.5	ENSP00000360619.3		Q13469-2

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

63893

AN:

140292

Hom.:

14455

Cov.:

show subpopulations

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.:

AF XY:

0.321

AC XY:

151764

AN XY:

472804

show subpopulations

African (AFR)

AF:

0.463

AC:

9188

AN:

19834

American (AMR)

AF:

0.380

AC:

14336

AN:

37746

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

6499

AN:

19466

East Asian (EAS)

AF:

0.364

AC:

11564

AN:

31752

South Asian (SAS)

AF:

0.290

AC:

20183

AN:

69708

European-Finnish (FIN)

AF:

0.302

AC:

12305

AN:

40714

Middle Eastern (MID)

AF:

0.289

AC:

915

AN:

3164

European-Non Finnish (NFE)

AF:

0.315

AC:

208302

AN:

661968

Other (OTH)

AF:

0.336

AC:

13421

AN:

39984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

8916

17831

26747

35662

44578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.456

AC:

63950

AN:

140366

Hom.:

14480

Cov.:

AF XY:

0.450

AC XY:

30514

AN XY:

67806

show subpopulations

African (AFR)

AF:

0.590

AC:

21932

AN:

37176

American (AMR)

AF:

0.448

AC:

6259

AN:

13978

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1320

AN:

3338

East Asian (EAS)

AF:

0.406

AC:

1931

AN:

4760

South Asian (SAS)

AF:

0.356

AC:

1503

AN:

4224

European-Finnish (FIN)

AF:

0.362

AC:

3170

AN:

8756

Middle Eastern (MID)

AF:

0.379

AC:

107

AN:

282

European-Non Finnish (NFE)

AF:

0.407

AC:

26468

AN:

65052

Other (OTH)

AF:

0.454

AC:

875

AN:

1926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1411

2822

4234

5645

7056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.176

Hom.:

350

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Below is the list of publications found by LitVar. It may be empty.

20-51391469-A-AG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over