Variant rs139312964 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.1239+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,613,906 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 94 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

ZIC2
NM_007129.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.81

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=-0.41).

BP6

Variant 13-99985127-G-A is Benign according to our data. Variant chr13-99985127-G-A is described in ClinVar as [Benign]. Clinvar id is 260129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-99985127-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
ZIC2	NM_007129.5 linkuse as main transcript	c.1239+18G>A		intron_variant		ENST00000376335.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ZIC2	ENST00000376335.8 linkuse as main transcript	c.1239+18G>A	intron_variant	1	NM_007129.5	P1
ZIC2	ENST00000468291.1 linkuse as main transcript	n.213+18G>A	intron_variant, non_coding_transcript_variant	2
ZIC2	ENST00000477213.1 linkuse as main transcript	n.321+18G>A	intron_variant, non_coding_transcript_variant	2
ZIC2	ENST00000490085.5 linkuse as main transcript	n.285+18G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2895

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00549

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

GnomAD3 exomes

AF:

0.00486

AC:

1219

AN:

250894

Hom.:

AF XY:

0.00358

AC XY:

486

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.0662

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00189

AC:

2763

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1188

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0680

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.0191

AC:

2906

AN:

152312

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1354

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0669

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00945

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Jan 31, 2024

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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