Variant 8-17156808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.128

Variant links:

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]

ZDHHC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZDHHC2	NM_016353.5 linkuse as main transcript	c.85C>T	p.Leu29=	synonymous_variant	1/13	ENST00000262096.13	NP_057437.1
ZDHHC2	XM_011544544.4 linkuse as main transcript	c.98C>T	p.Pro33Leu	missense_variant	1/15		XP_011542846.1
ZDHHC2	XM_011544545.4 linkuse as main transcript	c.98C>T	p.Pro33Leu	missense_variant	1/14		XP_011542847.1
ZDHHC2	XM_011544549.4 linkuse as main transcript	c.98C>T	p.Pro33Leu	missense_variant	1/9		XP_011542851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC2	ENST00000262096.13 linkuse as main transcript	c.85C>T	p.Leu29=	synonymous_variant	1/13	1	NM_016353.5	ENSP00000262096	P1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

163

AN:

151540

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00111

AC XY:

AN XY:

69232

show subpopulations

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.:

Cov.:

AF XY:

0.00132

AC XY:

894

AN XY:

676000

show subpopulations

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.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74116

show subpopulations

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.:

Bravo

AF:

0.000979

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over