Genetic Variant ZDHHC2:p.Leu29Leu (chr8-17156808-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016353.5(ZDHHC2):c.85C>T(p.Leu29Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,522,474 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

ZDHHC2
NM_016353.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.128

Publications

0 publications found

Variant links:

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]

ZDHHC2 links:

ENSG00000298219 (HGNC:):

ENSG00000298219 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 8-17156808-C-T is Benign according to our data. Variant chr8-17156808-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658443.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.128 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016353.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC2	NM_016353.5	MANE Select	c.85C>T	p.Leu29Leu	synonymous	Exon 1 of 13	NP_057437.1	Q9UIJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC2	ENST00000262096.13	TSL:1 MANE Select	c.85C>T	p.Leu29Leu	synonymous	Exon 1 of 13	ENSP00000262096.8	Q9UIJ5
ZDHHC2	ENST00000955296.1		c.85C>T	p.Leu29Leu	synonymous	Exon 1 of 15	ENSP00000625355.1
ZDHHC2	ENST00000955297.1		c.85C>T	p.Leu29Leu	synonymous	Exon 1 of 12	ENSP00000625356.1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

163

AN:

151540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00867

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.00110

AC:

140

AN:

127824

AF XY:

0.00111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000468

Gnomad ASJ exome

AF:

0.00710

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000281

GnomAD4 exome

AF:

0.00133

AC:

1828

AN:

1370826

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

894

AN XY:

676000

show subpopulations

African (AFR)

AF:

0.0000690

AC:

AN:

28998

American (AMR)

AF:

0.000274

AC:

AN:

32894

Ashkenazi Jewish (ASJ)

AF:

0.00834

AC:

203

AN:

24346

East Asian (EAS)

AF:

0.00

AC:

AN:

33048

South Asian (SAS)

AF:

0.00

AC:

AN:

76702

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

46626

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00135

AC:

1438

AN:

1065938

Other (OTH)

AF:

0.00178

AC:

101

AN:

56690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

184

275

367

459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

151648

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74116

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41468

American (AMR)

AF:

0.000327

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00867

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00199

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

67698

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.000979

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.13

PromoterAI

-0.0021

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over