rs966473

Variant names:

• chr8-17172612-A-G
• rs966473
• NM_016353.5:c.131-12177A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-17172612-A-G
• chr8-17172612-A-T

Variant summary

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

The NM_016353.5(ZDHHC2):​c.131-12177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,102 control chromosomes in the GnomAD database, including 17,632 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 0.44 (17632 hom., cov: 32)
• Consequence: ZDHHC2 NM_016353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC2	NM_016353.5	c.131-12177A>G		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.131-12177A>G		intron_variant	Intron 1 of 12	1	NM_016353.5	ENSP00000262096.8
ZDHHC2	ENST00000522184.1	c.-6+9723A>G		intron_variant	Intron 1 of 6	3		ENSP00000430317.1
ZDHHC2	ENST00000523132.1	c.-5-12177A>G		intron_variant	Intron 1 of 1	5		ENSP00000430804.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66468 AN: 151984 Hom.: 17628 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.437 AC: 66482 AN: 152102 Hom.: 17632 Cov.: 32 AF XY: 0.433 AC XY: 32161 AN XY: 74330

African (AFR) AF: 0.153 AC: 6356 AN: 41510

American (AMR) AF: 0.407 AC: 6221 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1706 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1182 AN: 5176

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4820

European-Finnish (FIN) AF: 0.550 AC: 5813 AN: 10564

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41647 AN: 67954

Other (OTH) AF: 0.434 AC: 918 AN: 2114

Alfa AF: 0.523 Hom.: 36610

Bravo AF: 0.411

Asia WGS AF: 0.262 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.6
DANN	Benign	0.67
PhyloP100		0.33
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: rs966473; hg19: chr8-17030121;