2-184936178-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_194250.2(ZNF804A):​c.782A>T​(p.Gln261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 1,613,750 control chromosomes in the GnomAD database, including 322,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.60 ( 28002 hom., cov: 32)
Exomes 𝑓: 0.63 ( 294493 hom. )

Consequence

ZNF804A
NM_194250.2 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.151
Variant links:
Genes affected
ZNF804A (HGNC:21711): (zinc finger protein 804A) The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.1170101E-6).
BP6
Variant 2-184936178-A-T is Benign according to our data. Variant chr2-184936178-A-T is described in ClinVar as [Benign]. Clinvar id is 1221151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF804ANM_194250.2 linkuse as main transcriptc.782A>T p.Gln261Leu missense_variant 4/4 ENST00000302277.7 NP_919226.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF804AENST00000302277.7 linkuse as main transcriptc.782A>T p.Gln261Leu missense_variant 4/41 NM_194250.2 ENSP00000303252 P1

Frequencies

GnomAD3 genomes
AF:
0.599
AC:
90997
AN:
151928
Hom.:
27995
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.465
Gnomad AMI
AF:
0.465
Gnomad AMR
AF:
0.710
Gnomad ASJ
AF:
0.704
Gnomad EAS
AF:
0.831
Gnomad SAS
AF:
0.616
Gnomad FIN
AF:
0.652
Gnomad MID
AF:
0.595
Gnomad NFE
AF:
0.624
Gnomad OTH
AF:
0.619
GnomAD3 exomes
AF:
0.656
AC:
164749
AN:
251092
Hom.:
55061
AF XY:
0.653
AC XY:
88576
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.465
Gnomad AMR exome
AF:
0.756
Gnomad ASJ exome
AF:
0.704
Gnomad EAS exome
AF:
0.842
Gnomad SAS exome
AF:
0.624
Gnomad FIN exome
AF:
0.668
Gnomad NFE exome
AF:
0.625
Gnomad OTH exome
AF:
0.657
GnomAD4 exome
AF:
0.632
AC:
924106
AN:
1461704
Hom.:
294493
Cov.:
64
AF XY:
0.632
AC XY:
459796
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.457
Gnomad4 AMR exome
AF:
0.750
Gnomad4 ASJ exome
AF:
0.695
Gnomad4 EAS exome
AF:
0.850
Gnomad4 SAS exome
AF:
0.628
Gnomad4 FIN exome
AF:
0.663
Gnomad4 NFE exome
AF:
0.623
Gnomad4 OTH exome
AF:
0.626
GnomAD4 genome
AF:
0.599
AC:
91041
AN:
152046
Hom.:
28002
Cov.:
32
AF XY:
0.603
AC XY:
44784
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.465
Gnomad4 AMR
AF:
0.710
Gnomad4 ASJ
AF:
0.704
Gnomad4 EAS
AF:
0.831
Gnomad4 SAS
AF:
0.619
Gnomad4 FIN
AF:
0.652
Gnomad4 NFE
AF:
0.624
Gnomad4 OTH
AF:
0.612
Alfa
AF:
0.629
Hom.:
22845
Bravo
AF:
0.601
TwinsUK
AF:
0.622
AC:
2307
ALSPAC
AF:
0.642
AC:
2474
ESP6500AA
AF:
0.479
AC:
2109
ESP6500EA
AF:
0.629
AC:
5404
ExAC
AF:
0.645
AC:
78267
Asia WGS
AF:
0.666
AC:
2316
AN:
3478
EpiCase
AF:
0.624
EpiControl
AF:
0.634

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 14, 2020This variant is associated with the following publications: (PMID: 24315717) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.84
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.27
DANN
Benign
0.94
DEOGEN2
Benign
0.0039
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0036
N
LIST_S2
Benign
0.024
T;T
MetaRNN
Benign
0.0000011
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.8
N;.
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.73
N;.
REVEL
Benign
0.062
Sift
Benign
0.37
T;.
Sift4G
Benign
0.31
T;T
Polyphen
0.0
B;.
Vest4
0.018
MPC
0.035
ClinPred
0.0039
T
GERP RS
0.19
Varity_R
0.062
gMVP
0.066

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: rs12476147; hg19: chr2-185800905; API