rs1555370794
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_177438.3(DICER1):c.2562C>A(p.Phe854Leu) variant causes a missense change involving the alteration of a non-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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F854Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.2562C>A | p.Phe854Leu | missense_variant | 16/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.2562C>A | p.Phe854Leu | missense_variant | 16/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class 0"). This variant has not been reported in the literature in individuals with DICER1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 854 of the DICER1 protein (p.Phe854Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at