chr2-144396406-T-A
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_014795.4(ZEB2):c.3067+6A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,612,920 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0072 ( 41 hom., cov: 32)
Exomes 𝑓: 0.0042 ( 273 hom. )
Consequence
ZEB2
NM_014795.4 splice_donor_region, intron
NM_014795.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.003162
2
Clinical Significance
Conservation
PhyloP100: 1.18
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 -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 2-144396406-T-A is Benign according to our data. Variant chr2-144396406-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 95633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-144396406-T-A is described in Lovd as [Benign]. Variant chr2-144396406-T-A is described in Lovd as [Likely_benign].
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0953 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.3067+6A>T | splice_donor_region_variant, intron_variant | ENST00000627532.3 | |||
ZEB2 | NM_001171653.2 | c.2995+6A>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.3067+6A>T | splice_donor_region_variant, intron_variant | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00715 AC: 1088AN: 152232Hom.: 40 Cov.: 32
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GnomAD3 exomes AF: 0.0173 AC: 4349AN: 251452Hom.: 227 AF XY: 0.0132 AC XY: 1789AN XY: 135902
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GnomAD4 exome AF: 0.00422 AC: 6160AN: 1460570Hom.: 273 Cov.: 32 AF XY: 0.00364 AC XY: 2645AN XY: 726626
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GnomAD4 genome AF: 0.00717 AC: 1092AN: 152350Hom.: 41 Cov.: 32 AF XY: 0.00776 AC XY: 578AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2012 | 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) | Dec 17, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics | Mar 02, 2015 | This variant was interpreted as benign based on ACMG evidence categories BS1 BS2. - |
Benign, no assertion criteria provided | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jan 30, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 16, 2020 | - - |
Mowat-Wilson syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 10, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Dec 09, 2014 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at