rs2023628

chr8-17189625-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZDHHC2	NM_016353.5	c.252+3200T>C		intron_variant		ENST00000262096.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.252+3200T>C		intron_variant		1	NM_016353.5	P1
ZDHHC2	ENST00000522184.1	c.117+3200T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.642

Alfa AF: 0.703 Hom.: 39127

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

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: rs2023628; hg19: chr8-17047134;