rs182192729

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007129.5(ZIC2):c.1326C>T(p.Ser442Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,595,700 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 95 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 82 hom. )

Consequence

ZIC2
NM_007129.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.834

Publications

1 publications found

Variant links:

Genes affected

ZIC2 (HGNC:12873): (Zic family member 2) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]

ZIC2 Gene-Disease associations (from GenCC):

holoprosencephaly 5
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ZIC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 13-99985409-C-T is Benign according to our data. Variant chr13-99985409-C-T is described in ClinVar as Benign. ClinVar VariationId is 196447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.834 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC2	NM_007129.5 link	c.1326C>T	p.Ser442Ser	synonymous_variant	Exon 3 of 3	ENST00000376335.8	NP_009060.2	O95409A0A024RDY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC2	ENST00000376335.8 link	c.1326C>T	p.Ser442Ser	synonymous_variant	Exon 3 of 3	1	NM_007129.5	ENSP00000365514.3		O95409

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2893

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00462

AC:

1046

AN:

226342

AF XY:

0.00359

show subpopulations

Gnomad AFR exome

AF:

0.0670

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.000827

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000963

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00190

AC:

2750

AN:

1443666

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1183

AN XY:

718614

show subpopulations

African (AFR)

AF:

0.0680

AC:

2267

AN:

33350

American (AMR)

AF:

0.00301

AC:

134

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.000769

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.000128

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37932

Middle Eastern (MID)

AF:

0.00227

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1110240

Other (OTH)

AF:

0.00410

AC:

246

AN:

60046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0191

AC:

2904

AN:

152034

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1355

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0670

AC:

2779

AN:

41500

American (AMR)

AF:

0.00556

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67956

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00948

Hom.:

Bravo

AF:

0.0211

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 13, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 5

Benign:2

Nov 06, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32022405) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.7

(source)

DANN

Benign

0.93

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over