2-184668853-T-C

Variant names:

• chr2-184668853-T-C
• rs7597593
• NM_194250.2:c.111+69783T>C

Variant summary

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

The NM_194250.2(ZNF804A):​c.111+69783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,742 control chromosomes in the GnomAD database, including 22,399 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 0.53 (22399 hom., cov: 31)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 38 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.111+69783T>C		intron_variant	Intron 1 of 3	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.111+69783T>C		intron_variant	Intron 1 of 3	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80480 AN: 151622 Hom.: 22402 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.530 AC: 80482 AN: 151742 Hom.: 22399 Cov.: 31 AF XY: 0.529 AC XY: 39189 AN XY: 74134

African (AFR) AF: 0.358 AC: 14837 AN: 41464

American (AMR) AF: 0.574 AC: 8715 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2869 AN: 5160

South Asian (SAS) AF: 0.489 AC: 2356 AN: 4814

European-Finnish (FIN) AF: 0.606 AC: 6386 AN: 10546

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41395 AN: 67782

Other (OTH) AF: 0.526 AC: 1113 AN: 2114

Alfa AF: 0.582 Hom.: 92849

Bravo AF: 0.524

Asia WGS AF: 0.503 AC: 1748 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		0.22
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: rs7597593; hg19: chr2-185533580;