Variant chr13-99983123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_007129.5(ZIC2):c.1059C>T(p.His353=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC2	NM_007129.5 linkuse as main transcript	c.1059C>T	p.His353=	synonymous_variant	1/3	ENST00000376335.8	NP_009060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC2	ENST00000376335.8 linkuse as main transcript	c.1059C>T	p.His353=	synonymous_variant	1/3	1	NM_007129.5	ENSP00000365514	P1

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

GnomAD3 exomes

AF:

0.0812

AC:

20362

AN:

250680

Hom.:

1142

AF XY:

0.0823

AC XY:

11171

AN XY:

135670

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 SAS exome

AF:

0.0284

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

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.0640

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0889

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0774

AC:

11750

AN:

151884

Hom.:

591

Cov.:

AF XY:

0.0748

AC XY:

5556

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.000782

Gnomad4 SAS

AF:

0.0279

Gnomad4 FIN

AF:

0.0821

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.0964

Alfa

AF:

0.0979

Hom.:

460

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Holoprosencephaly 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.66

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