8-17207973-A-G

Position:

• chr8-17207973-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016353.5(ZDHHC2):​c.611A>G​(p.Asp204Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZDHHC2 NM_016353.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC2	NM_016353.5	c.611A>G	p.Asp204Gly	missense_variant	8/13	ENST00000262096.13	NP_057437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.611A>G	p.Asp204Gly	missense_variant	8/13	1	NM_016353.5	ENSP00000262096	P1
ZDHHC2	ENST00000517334.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2021

The c.611A>G (p.D204G) alteration is located in exon 8 (coding exon 8) of the ZDHHC2 gene. This alteration results from a A to G substitution at nucleotide position 611, causing the aspartic acid (D) at amino acid position 204 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.33
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.40		Gain of catalytic residue at D204 (P = 0.0857);
MVP		0.32
MPC		0.18
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr8-17065482;