8-17156803-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_016353.5(ZDHHC2):c.80C>G(p.Thr27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,370,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZDHHC2 NM_016353.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10760656).
• BP6: Variant 8-17156803-C-G is Benign according to our data. Variant chr8-17156803-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2524072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC2	NM_016353.5	c.80C>G	p.Thr27Ser	missense_variant	1/13	ENST00000262096.13
ZDHHC2	XM_011544544.4	c.93C>G	p.His31Gln	missense_variant	1/15
ZDHHC2	XM_011544545.4	c.93C>G	p.His31Gln	missense_variant	1/14
ZDHHC2	XM_011544549.4	c.93C>G	p.His31Gln	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.80C>G	p.Thr27Ser	missense_variant	1/13	1	NM_016353.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1370714 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 676006

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: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	15
Dann	Benign	0.30
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.14	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.56		Gain of MoRF binding (P = 0.0975);
MVP		0.31
MPC		0.019
ClinPred		0.055	T
GERP RS		1.7
Varity_R		0.025
gMVP		0.24

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.

Other links and lift over

hg19: chr8-17014312;