rs757981529
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM4_SupportingBP6
The NM_001348768.2(HECW2):c.2270_2272del(p.Glu757del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000379 in 1,584,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
HECW2
NM_001348768.2 inframe_deletion
NM_001348768.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.24
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 Uncertain_significance. Variant got 0 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001348768.2. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 2-196318617-CCTT-C is Benign according to our data. Variant chr2-196318617-CCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 254099.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HECW2 | NM_001348768.2 | c.2270_2272del | p.Glu757del | inframe_deletion | 9/29 | ENST00000644978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HECW2 | ENST00000644978.2 | c.2270_2272del | p.Glu757del | inframe_deletion | 9/29 | NM_001348768.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000133 AC: 3AN: 224938Hom.: 0 AF XY: 0.00000828 AC XY: 1AN XY: 120768
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GnomAD4 exome AF: 0.00000279 AC: 4AN: 1432564Hom.: 0 AF XY: 0.00000281 AC XY: 2AN XY: 710756
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Oromandibular-limb hypogenesis spectrum Benign:1
Likely benign, no assertion criteria provided | research | CHU Sainte-Justine Research Center, University of Montreal | Aug 12, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at