8-17169343-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.130+12490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,516 control chromosomes in the GnomAD database, including 19,042 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 0.48 (19042 hom., cov: 29)
• Consequence: ZDHHC2 NM_016353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC2	NM_016353.5	c.130+12490T>C		intron_variant		ENST00000262096.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.130+12490T>C		intron_variant		1	NM_016353.5	P1
ZDHHC2	ENST00000522184.1	c.-6+6454T>C		intron_variant		3
ZDHHC2	ENST00000523132.1	c.-6+11770T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73003 AN: 151398 Hom.: 19002 Cov.: 29

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.482 AC: 73098 AN: 151516 Hom.: 19042 Cov.: 29 AF XY: 0.492 AC XY: 36401 AN XY: 74012

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.502

Alfa AF: 0.394 Hom.: 16750

Bravo AF: 0.498

Asia WGS AF: 0.745 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.1
Dann	Benign	0.84

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: rs2959634; hg19: chr8-17026852;