rs189469383
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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
NM_007129.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.43
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]
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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 | 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 | c.213G>A | p.Pro71= | synonymous_variant | 1/3 | 1 | NM_007129.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00305 AC: 462AN: 151474Hom.: 3 Cov.: 31
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GnomAD3 exomes AF: 0.000505 AC: 53AN: 104954Hom.: 0 AF XY: 0.000467 AC XY: 28AN XY: 59912
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GnomAD4 exome AF: 0.000321 AC: 431AN: 1343930Hom.: 6 Cov.: 31 AF XY: 0.000294 AC XY: 195AN XY: 663982
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GnomAD4 genome ? AF: 0.00305 AC: 463AN: 151582Hom.: 3 Cov.: 31 AF XY: 0.00319 AC XY: 236AN XY: 74092
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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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at