chr2-184936832-A-T

Variant names:

• chr2-184936832-A-T
• rs35676856
• NM_194250.2:c.1436A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194250.2(ZNF804A):​c.1436A>T​(p.Asp479Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D479G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF804A NM_194250.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0664013).

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.1436A>T	p.Asp479Val	missense	Exon 4 of 4	NP_919226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.1436A>T	p.Asp479Val	missense	Exon 4 of 4	ENSP00000303252.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.49
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.45
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.013
Sift	Benign	0.27	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.22		Loss of helix (P = 0.0093)
MVP		0.043
MPC		0.044
ClinPred		0.034	T
GERP RS		1.5
Varity_R		0.088
gMVP		0.14
Mutation Taster		=95/5	polymorphism

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: rs35676856; hg19: chr2-185801559;