2-184915498-G-A

Variant names:

• chr2-184915498-G-A
• rs13423388
• NM_194250.2:c.256-18105G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194250.2(ZNF804A):​c.256-18105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,950 control chromosomes in the GnomAD database, including 1,756 homozygotes. 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: 𝑓 0.15 (1756 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 5 publications found

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]

ZNF804A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194250.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	NM_194250.2	MANE Select	c.256-18105G>A		intron	N/A	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.256-18105G>A		intron	N/A	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22056 AN: 151832 Hom.: 1752 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.145 AC: 22072 AN: 151950 Hom.: 1756 Cov.: 32 AF XY: 0.142 AC XY: 10526 AN XY: 74264

African (AFR) AF: 0.177 AC: 7339 AN: 41484

American (AMR) AF: 0.111 AC: 1690 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5172

South Asian (SAS) AF: 0.0910 AC: 438 AN: 4814

European-Finnish (FIN) AF: 0.0936 AC: 990 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10338 AN: 67890

Other (OTH) AF: 0.143 AC: 301 AN: 2108

Alfa AF: 0.152 Hom.: 244

Bravo AF: 0.147

Asia WGS AF: 0.0630 AC: 219 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13423388; hg19: chr2-185780225;