GeneBe

rs778032939

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_007129.5(ZIC2):​c.54G>A​(p.Ala18Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A18A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZIC2
NM_007129.5 synonymous

Scores

1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0360

Publications

0 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
  • holoprosencephaly
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP7
Synonymous conserved (PhyloP=0.036 with no splicing effect.

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ZIC2
NM_007129.5
MANE Select
c.54G>Ap.Ala18Ala
synonymous
Exon 1 of 3NP_009060.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ZIC2
ENST00000376335.8
TSL:1 MANE Select
c.54G>Ap.Ala18Ala
synonymous
Exon 1 of 3ENSP00000365514.3O95409

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1142874
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
548288
African (AFR)
AF:
0.00
AC:
0
AN:
23186
American (AMR)
AF:
0.00
AC:
0
AN:
9158
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15442
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26728
South Asian (SAS)
AF:
0.00
AC:
0
AN:
34976
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25336
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3672
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
958046
Other (OTH)
AF:
0.00
AC:
0
AN:
46330
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
15
DANN
Uncertain
0.98
PhyloP100
0.036
PromoterAI
0.013
Neutral

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

Other links and lift over

dbSNP: rs778032939; hg19: chr13-100634372; API