rs2023628

Variant names:

• chr8-17189625-T-C
• rs2023628
• NM_016353.5:c.252+3200T>C

Variant summary

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

The NM_016353.5(ZDHHC2):​c.252+3200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,996 control chromosomes in the GnomAD database, including 33,412 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 0.65 (33412 hom., cov: 32)
• Consequence: ZDHHC2 NM_016353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718
• Publications: 4 publications found

Genes affected

ZDHHC2 (HGNC:18469): (zinc finger DHHC-type palmitoyltransferase 2) Enables protein homodimerization activity and protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including peptidyl-L-cysteine S-palmitoylation; regulation of protein catabolic process; and regulation of protein localization to plasma membrane. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC2	NM_016353.5	c.252+3200T>C		intron_variant	Intron 3 of 12	ENST00000262096.13	NP_057437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.252+3200T>C		intron_variant	Intron 3 of 12	1	NM_016353.5	ENSP00000262096.8
ZDHHC2	ENST00000522184.1	c.117+3200T>C		intron_variant	Intron 3 of 6	3		ENSP00000430317.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99026 AN: 151878 Hom.: 33382 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.652 AC: 99095 AN: 151996 Hom.: 33412 Cov.: 32 AF XY: 0.650 AC XY: 48288 AN XY: 74292

African (AFR) AF: 0.514 AC: 21315 AN: 41432

American (AMR) AF: 0.740 AC: 11300 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2000 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2228 AN: 5140

South Asian (SAS) AF: 0.439 AC: 2121 AN: 4830

European-Finnish (FIN) AF: 0.753 AC: 7959 AN: 10570

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50011 AN: 67972

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.698 Hom.: 60533

Bravo AF: 0.649

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		0.72
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: rs2023628; hg19: chr8-17047134;