rs4533485
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001348768.2(HECW2):c.3530-985G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 23)
Failed GnomAD Quality Control
Consequence
HECW2
NM_001348768.2 intron
NM_001348768.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.932
Genes affected
HECW2 (HGNC:29853): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) This gene encodes a member of a family of E3 ubiquitin ligases which plays an important role in the proliferation, migration and differentiation of neural crest cells as a regulator of glial cell line-derived neurotrophic factor (GDNF)/Ret signaling. This gene also plays an important role in angiogenesis through stabilization of endothelial cell-to-cell junctions as a regulator of angiomotin-like 1 stability. The encoded protein contains an N-terminal calcium/lipid-binding (C2) domain involved in membrane targeting, two-four WW domains responsible for cellular localization and substrate recognition, and a C-terminal homologous with E6-associated protein C-terminus (HECT) catalytic domain. Naturally occurring mutations in this gene are associated with neurodevelopmental delay, hypotonia, and epilepsy. The decreased expression of this gene in the aganglionic colon is associated with Hirschsprung's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HECW2 | NM_001348768.2 | c.3530-985G>T | intron_variant | ENST00000644978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HECW2 | ENST00000644978.2 | c.3530-985G>T | intron_variant | NM_001348768.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 147140Hom.: 0 Cov.: 23 FAILED QC
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 147140Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 71306
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ClinVar
Not reported inComputational scores
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Name
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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