NM_007129.5:c.1059C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_007129.5(ZIC2):c.1059C>T(p.His353His) variant causes a synonymous change. The variant allele was found at a frequency of 0.0996 in 1,613,394 control chromosomes in the GnomAD database, including 9,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 591 hom., cov: 31)

Exomes 𝑓: 0.10 ( 8583 hom. )

Consequence

ZIC2
NM_007129.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.17

Publications

15 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 13-99983123-C-T is Benign according to our data. Variant chr13-99983123-C-T is described in ClinVar as Benign. ClinVar VariationId is 95446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007129.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC2	NM_007129.5	MANE Select	c.1059C>T	p.His353His	synonymous	Exon 1 of 3	NP_009060.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC2	ENST00000376335.8	TSL:1 MANE Select	c.1059C>T	p.His353His	synonymous	Exon 1 of 3	ENSP00000365514.3

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11752

AN:

151764

Hom.:

592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0881

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.000781

Gnomad SAS

AF:

0.0277

Gnomad FIN

AF:

0.0821

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.0979

GnomAD2 exomes

AF:

0.0812

AC:

20362

AN:

250680

AF XY:

0.0823

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.0607

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0847

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.102

AC:

148931

AN:

1461510

Hom.:

8583

Cov.:

AF XY:

0.100

AC XY:

72787

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.0163

AC:

547

AN:

33464

American (AMR)

AF:

0.0640

AC:

2861

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4418

AN:

26104

East Asian (EAS)

AF:

0.000202

AC:

AN:

39698

South Asian (SAS)

AF:

0.0297

AC:

2563

AN:

86252

European-Finnish (FIN)

AF:

0.0889

AC:

4737

AN:

53282

Middle Eastern (MID)

AF:

0.105

AC:

608

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

127133

AN:

1111884

Other (OTH)

AF:

0.100

AC:

6056

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9132

18263

27395

36526

45658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4496

8992

13488

17984

22480

<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:

0.0774

AC:

11750

AN:

151884

Hom.:

591

Cov.:

AF XY:

0.0748

AC XY:

5556

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.0205

AC:

848

AN:

41434

American (AMR)

AF:

0.0880

AC:

1343

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

564

AN:

3464

East Asian (EAS)

AF:

0.000782

AC:

AN:

5112

South Asian (SAS)

AF:

0.0279

AC:

134

AN:

4802

European-Finnish (FIN)

AF:

0.0821

AC:

869

AN:

10588

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7647

AN:

67914

Other (OTH)

AF:

0.0964

AC:

203

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

533

1066

1599

2132

2665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0842

Hom.:

602

Bravo

AF:

0.0757

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 08, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Holoprosencephaly 5

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

6.2

Mutation Taster

=33/67

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over