2-184936112-A-T

Position:

• chr2-184936112-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194250.2(ZNF804A):​c.716A>T​(p.Asp239Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF804A NM_194250.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32274473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.716A>T	p.Asp239Val	missense_variant	4/4	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.716A>T	p.Asp239Val	missense_variant	4/4	1	NM_194250.2	ENSP00000303252.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.716A>T (p.D239V) alteration is located in exon 4 (coding exon 4) of the ZNF804A gene. This alteration results from a A to T substitution at nucleotide position 716, causing the aspartic acid (D) at amino acid position 239 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.9	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	D;.
Vest4		0.65
MutPred		0.29		Gain of MoRF binding (P = 0.0273);.;
MVP		0.28
MPC		0.30
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.35
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-185800839;