8-17207344-T-C

Variant names:

• chr8-17207344-T-C
• rs6997380
• NM_016353.5:c.598-616T>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.598-616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,072 control chromosomes in the GnomAD database, including 6,798 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 0.29 (6798 hom., cov: 32)
• Consequence: ZDHHC2 NM_016353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016353.5. 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
	ZDHHC2	NM_016353.5	MANE Select	c.598-616T>C		intron	N/A	NP_057437.1
	ZDHHC2	NM_001362988.2		c.514-616T>C		intron	N/A	NP_001349917.1
	ZDHHC2	NM_001362989.2		c.463-616T>C		intron	N/A	NP_001349918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC2	ENST00000262096.13	TSL:1 MANE Select	c.598-616T>C		intron	N/A	ENSP00000262096.8

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44253 AN: 151954 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.291 AC: 44274 AN: 152072 Hom.: 6798 Cov.: 32 AF XY: 0.296 AC XY: 22003 AN XY: 74340

African (AFR) AF: 0.347 AC: 14396 AN: 41482

American (AMR) AF: 0.345 AC: 5266 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2110 AN: 5154

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4822

European-Finnish (FIN) AF: 0.296 AC: 3130 AN: 10574

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15860 AN: 67972

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.266 Hom.: 14844

Bravo AF: 0.300

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		-0.44
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: rs6997380; hg19: chr8-17064853;