chr2-196220104-A-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_001348768.2(HECW2):c.4343T>C(p.Leu1448Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1448W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001348768.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HECW2 | NM_001348768.2 | c.4343T>C | p.Leu1448Ser | missense_variant | 26/29 | ENST00000644978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HECW2 | ENST00000644978.2 | c.4343T>C | p.Leu1448Ser | missense_variant | 26/29 | NM_001348768.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with hypotonia, seizures, and absent language Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Oct 02, 2021 | The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Leu1448Trp) has been reported as likely pathogenic (ClinVar ID: VCV000801845.1, PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.762, 3Cnet: 0.964, PP3). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.