2-184902089-A-G

Position:

• chr2-184902089-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000302277.7(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 ENST00000302277.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.256-31514A>G		intron_variant		ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.256-31514A>G		intron_variant		1	NM_194250.2	ENSP00000303252.6
RPL23AP33	ENST00000442301.2	n.*22T>C		downstream_gene_variant		6

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.643

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.453

Alfa AF: 0.497 Hom.: 18145

Bravo AF: 0.424

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs7603001; hg19: chr2-185766816;