rs587776610
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_014795.4(ZEB2):βc.298_300delβ(p.Asn100del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000124 in 1,613,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. N100N) has been classified as Likely benign.
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 32)
Exomes π: 0.000012 ( 0 hom. )
Consequence
ZEB2
NM_014795.4 inframe_deletion
NM_014795.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.55
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 Likely_benign. Variant got -3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_014795.4. Strenght limited to Supporting due to length of the change: 1aa.
BS2
?
High AC in GnomAdExome4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.298_300del | p.Asn100del | inframe_deletion | 3/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.298_300del | p.Asn100del | inframe_deletion | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.298_300del | p.Asn100del | inframe_deletion | 3/10 | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250866Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135610
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461582Hom.: 0 AF XY: 0.0000124 AC XY: 9AN XY: 727082
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74302
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mowat-Wilson syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 4764). This variant has been observed in individual(s) with mild clinical features of ZEB2-related conditions (PMID: 12451214). This variant is present in population databases (rs587776610, gnomAD 0.03%). This variant, c.298_300del, results in the deletion of 1 amino acid(s) of the ZEB2 protein (p.Asn100del), but otherwise preserves the integrity of the reading frame. - |
Hirschsprung disease-intellectual disability syndrome, late infantile Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 26, 2002 | - - |
Computational scores
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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