8-17156808-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_016353.5(ZDHHC2):c.85C>T(p.Leu29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,522,474 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (4 hom.)
• Consequence: ZDHHC2 NM_016353.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 8-17156808-C-T is Benign according to our data. Variant chr8-17156808-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC2	NM_016353.5	c.85C>T	p.Leu29=	synonymous_variant	1/13	ENST00000262096.13
ZDHHC2	XM_011544544.4	c.98C>T	p.Pro33Leu	missense_variant	1/15
ZDHHC2	XM_011544545.4	c.98C>T	p.Pro33Leu	missense_variant	1/14
ZDHHC2	XM_011544549.4	c.98C>T	p.Pro33Leu	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.85C>T	p.Leu29=	synonymous_variant	1/13	1	NM_016353.5	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 163 AN: 151540 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00867

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00110 AC: 140 AN: 127824 Hom.: 1 AF XY: 0.00111 AC XY: 77 AN XY: 69232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000468

Gnomad ASJ exome AF: 0.00710

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000281

GnomAD4 exome AF: 0.00133 AC: 1828 AN: 1370826 Hom.: 4 Cov.: 31 AF XY: 0.00132 AC XY: 894 AN XY: 676000

Gnomad4 AFR exome AF: 0.0000690

Gnomad4 AMR exome AF: 0.000274

Gnomad4 ASJ exome AF: 0.00834

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00135

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00107 AC: 163 AN: 151648 Hom.: 0 Cov.: 32 AF XY: 0.00108 AC XY: 80 AN XY: 74116

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00867

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00199

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00160 Hom.: 0

Bravo AF: 0.000979

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

ZDHHC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	13
Dann	Benign	0.88

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: rs375504005; hg19: chr8-17014317; COSMIC: COSV100025039; COSMIC: COSV100025039;