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GeneBe

20-51432158-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_012340.5(NFATC2):c.2631C>T(p.Asn877=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,603,606 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 17 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 14 hom. )

Consequence

NFATC2
NM_012340.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.343
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-51432158-G-A is Benign according to our data. Variant chr20-51432158-G-A is described in ClinVar as [Benign]. Clinvar id is 777583.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.343 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00674 (1026/152290) while in subpopulation AFR AF= 0.0232 (964/41562). AF 95% confidence interval is 0.022. There are 17 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NFATC2NM_012340.5 linkuse as main transcriptc.2631C>T p.Asn877= synonymous_variant 9/11 ENST00000371564.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFATC2ENST00000371564.8 linkuse as main transcriptc.2631C>T p.Asn877= synonymous_variant 9/111 NM_012340.5 A1Q13469-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00670
AC:
1020
AN:
152172
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00175
AC:
432
AN:
246246
Hom.:
6
AF XY:
0.00111
AC XY:
147
AN XY:
132854
show subpopulations
Gnomad AFR exome
AF:
0.0240
Gnomad AMR exome
AF:
0.000762
Gnomad ASJ exome
AF:
0.000209
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000339
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000720
Gnomad OTH exome
AF:
0.000668
GnomAD4 exome
AF:
0.000651
AC:
945
AN:
1451316
Hom.:
14
Cov.:
31
AF XY:
0.000576
AC XY:
415
AN XY:
720246
show subpopulations
Gnomad4 AFR exome
AF:
0.0228
Gnomad4 AMR exome
AF:
0.00106
Gnomad4 ASJ exome
AF:
0.000234
Gnomad4 EAS exome
AF:
0.0000507
Gnomad4 SAS exome
AF:
0.0000821
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000290
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00674
AC:
1026
AN:
152290
Hom.:
17
Cov.:
32
AF XY:
0.00591
AC XY:
440
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0232
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00945
Alfa
AF:
0.00343
Hom.:
1
Bravo
AF:
0.00766
Asia WGS
AF:
0.00693
AC:
25
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
5.2
Dann
Benign
0.73

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs75923936; hg19: chr20-50048695; API