rs2959631

Variant names:

• chr8-17177000-G-A
• rs2959631
• NM_016353.5:c.131-7789G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016353.5(ZDHHC2):​c.131-7789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,144 control chromosomes in the GnomAD database, including 1,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1230 hom., cov: 32)
• Consequence: ZDHHC2 NM_016353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC2	NM_016353.5	c.131-7789G>A		intron_variant	Intron 1 of 12	ENST00000262096.13	NP_057437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.131-7789G>A		intron_variant	Intron 1 of 12	1	NM_016353.5	ENSP00000262096.8
ZDHHC2	ENST00000522184.1	c.-5-7789G>A		intron_variant	Intron 1 of 6	3		ENSP00000430317.1
ZDHHC2	ENST00000523132.1	c.-5-7789G>A		intron_variant	Intron 1 of 1	5		ENSP00000430804.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17634 AN: 152026 Hom.: 1230 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17636 AN: 152144 Hom.: 1230 Cov.: 32 AF XY: 0.118 AC XY: 8741 AN XY: 74378

African (AFR) AF: 0.171 AC: 7109 AN: 41488

American (AMR) AF: 0.107 AC: 1627 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3468

East Asian (EAS) AF: 0.160 AC: 828 AN: 5174

South Asian (SAS) AF: 0.184 AC: 885 AN: 4822

European-Finnish (FIN) AF: 0.0611 AC: 647 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5435 AN: 68014

Other (OTH) AF: 0.120 AC: 253 AN: 2106

Alfa AF: 0.0968 Hom.: 3038

Bravo AF: 0.122

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2959631; hg19: chr8-17034509;