rs6711223
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014795.4(ZEB2):c.930C>T(p.Tyr310=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,609,982 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 27 hom. )
Consequence
ZEB2
NM_014795.4 synonymous
NM_014795.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.222
Genes affected
ZEB2 (HGNC:14881): (zinc finger E-box binding homeobox 2) The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 2-144400257-G-A is Benign according to our data. Variant chr2-144400257-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 95643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-144400257-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.222 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1574/152316) while in subpopulation AFR AF= 0.0314 (1304/41566). AF 95% confidence interval is 0.03. There are 26 homozygotes in gnomad4. There are 783 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1574 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.930C>T | p.Tyr310= | synonymous_variant | 8/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.858C>T | p.Tyr286= | synonymous_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.930C>T | p.Tyr310= | synonymous_variant | 8/10 | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0103 AC: 1572AN: 152198Hom.: 26 Cov.: 32
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GnomAD3 exomes AF: 0.00393 AC: 963AN: 245024Hom.: 15 AF XY: 0.00318 AC XY: 425AN XY: 133444
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GnomAD4 exome AF: 0.00190 AC: 2768AN: 1457666Hom.: 27 Cov.: 32 AF XY: 0.00176 AC XY: 1277AN XY: 725310
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GnomAD4 genome ? AF: 0.0103 AC: 1574AN: 152316Hom.: 26 Cov.: 32 AF XY: 0.0105 AC XY: 783AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 05, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 21, 2013 | - - |
Mowat-Wilson syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | ZEB2: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 12, 2016 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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