rs3750249

Positions:

• chr8-17221849-A-G
• chr8-17221849-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016353.5(ZDHHC2):​c.*1628A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,082 control chromosomes in the GnomAD database, including 9,485 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 0.33 (9464 hom., cov: 32)
  • Exomes 𝑓: 0.28 (21 hom.)
• Consequence: ZDHHC2 NM_016353.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC2	NM_016353.5	c.*1628A>G		3_prime_UTR_variant	13/13	ENST00000262096.13	NP_057437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC2	ENST00000262096.13	c.*1628A>G		3_prime_UTR_variant	13/13	1	NM_016353.5	ENSP00000262096	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50357 AN: 151532 Hom.: 9448 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.275 AC: 119 AN: 432 Hom.: 21 Cov.: 0 AF XY: 0.296 AC XY: 77 AN XY: 260

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.332 AC: 50408 AN: 151650 Hom.: 9464 Cov.: 32 AF XY: 0.342 AC XY: 25377 AN XY: 74126

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.348

Alfa AF: 0.262 Hom.: 4435

Bravo AF: 0.346

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3750249; hg19: chr8-17079358;