Variant 8-17156790-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016353.5(ZDHHC2):c.67G>C(p.Val23Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,370,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ZDHHC2
NM_016353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38964254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZDHHC2	NM_016353.5 linkuse as main transcript	c.67G>C	p.Val23Leu	missense_variant	1/13	ENST00000262096.13	NP_057437.1
ZDHHC2	XM_011544544.4 linkuse as main transcript	c.80G>C	p.Gly27Ala	missense_variant	1/15		XP_011542846.1
ZDHHC2	XM_011544545.4 linkuse as main transcript	c.80G>C	p.Gly27Ala	missense_variant	1/14		XP_011542847.1
ZDHHC2	XM_011544549.4 linkuse as main transcript	c.80G>C	p.Gly27Ala	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.67G>C	p.Val23Leu	missense_variant	1/13	1	NM_016353.5	ENSP00000262096	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

675916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.38e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.67G>C (p.V23L) alteration is located in exon 1 (coding exon 1) of the ZDHHC2 gene. This alteration results from a G to C substitution at nucleotide position 67, causing the valine (V) at amino acid position 23 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.1

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.016

Polyphen

0.018

Vest4

0.29

MutPred

0.44

Gain of helix (P = 0.0696);

MVP

0.36

MPC

0.021

ClinPred

0.60

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.29

gMVP

0.80

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over