rs189469383

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_007129.5(ZIC2):c.213G>A(p.Pro71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,495,512 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 6 hom. )

Consequence

ZIC2
NM_007129.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.43

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-99982277-G-A is Benign according to our data. Variant chr13-99982277-G-A is described in ClinVar as [Benign]. Clinvar id is 260131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-99982277-G-A is described in Lovd as [Likely_benign]. Variant chr13-99982277-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.43 with no splicing effect.

BS2

High AC in GnomAd4 at 463 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZIC2	NM_007129.5 linkuse as main transcript	c.213G>A	p.Pro71=	synonymous_variant	1/3	ENST00000376335.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZIC2	ENST00000376335.8 linkuse as main transcript	c.213G>A	p.Pro71=	synonymous_variant	1/3	1	NM_007129.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

462

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

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:

0.0000737

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000505

AC:

AN:

104954

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

59912

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.000682

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000728

Gnomad OTH exome

AF:

0.000359

GnomAD4 exome

AF:

0.000321

AC:

431

AN:

1343930

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

195

AN XY:

663982

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000723

Gnomad4 ASJ exome

AF:

0.0000425

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.000849

GnomAD4 genome

AF:

0.00305

AC:

463

AN:

151582

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

236

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.00197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000630

Hom.:

Bravo

AF:

0.00370

Asia WGS

AF:

0.000586

AC:

AN:

3428

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Holoprosencephaly 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over