2-184902089-A-G

Variant names:

• chr2-184902089-A-G
• rs7603001
• NM_194250.2:c.256-31514A>G

Variant summary

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

The NM_194250.2(ZNF804A):​c.256-31514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,072 control chromosomes in the GnomAD database, including 16,866 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 0.43 (16845 hom., cov: 32)
  • Exomes 𝑓: 0.74 (21 hom.)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 18 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]

RPL23AP33 (HGNC:36946): (ribosomal protein L23a pseudogene 33)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 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.256-31514A>G		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.256-31514A>G		intron	N/A	ENSP00000303252.6
	RPL23AP33	ENST00000442301.2	TSL:6	n.*22T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64864 AN: 151874 Hom.: 16848 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.738 AC: 59 AN: 80 Hom.: 21 Cov.: 0 AF XY: 0.696 AC XY: 32 AN XY: 46

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.875 AC: 21 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.643 AC: 27 AN: 42

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.427 AC: 64866 AN: 151992 Hom.: 16845 Cov.: 32 AF XY: 0.432 AC XY: 32086 AN XY: 74270

African (AFR) AF: 0.122 AC: 5082 AN: 41498

American (AMR) AF: 0.606 AC: 9234 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4219 AN: 5150

South Asian (SAS) AF: 0.492 AC: 2364 AN: 4808

European-Finnish (FIN) AF: 0.553 AC: 5833 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34987 AN: 67954

Other (OTH) AF: 0.453 AC: 953 AN: 2106

Alfa AF: 0.494 Hom.: 21578

Bravo AF: 0.424

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.50
PhyloP100		-0.0050
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: rs7603001; hg19: chr2-185766816;