Variant 8-17184809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016353.5(ZDHHC2):c.151G>A(p.Glu51Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000331 in 1,548,936 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E51Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ZDHHC2
NM_016353.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25080293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC2	NM_016353.5 linkuse as main transcript	c.151G>A	p.Glu51Lys	missense_variant	2/13	ENST00000262096.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZDHHC2	ENST00000262096.13 linkuse as main transcript	c.151G>A	p.Glu51Lys	missense_variant	2/13	1	NM_016353.5	P1
ZDHHC2	ENST00000522184.1 linkuse as main transcript	c.16G>A	p.Glu6Lys	missense_variant	2/7	3
ZDHHC2	ENST00000523132.1 linkuse as main transcript	c.16G>A	p.Glu6Lys	missense_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000190

AC:

AN:

158250

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

83458

show subpopulations

Gnomad AFR exome

AF:

0.000119

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000351

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000338

AC:

472

AN:

1396886

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

229

AN XY:

689098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000636

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000409

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000263

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000329

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000277

AC:

ESP6500EA

AF:

0.000125

AC:

ExAC

AF:

0.0000401

AC:

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

Aug 26, 2022

The c.151G>A (p.E51K) alteration is located in exon 2 (coding exon 2) of the ZDHHC2 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glutamic acid (E) at amino acid position 51 to be replaced by a lysine (K). 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

Benign

0.14

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

-0.030

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.045

T;.;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;.;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.0

D;D;N

REVEL

Uncertain

0.31

Sift

Benign

0.23

T;.;T

Sift4G

Benign

0.26

T;.;T

Polyphen

0.38

B;.;.

Vest4

0.68

MVP

0.80

MPC

0.023

ClinPred

0.32

GERP RS

4.8

Varity_R

0.29

gMVP

0.67

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