rs749686370
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_177438.3(DICER1):c.1745T>C(p.Ile582Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I582F) has been classified as Uncertain significance.
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.1745T>C | p.Ile582Thr | missense_variant | 10/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.1745T>C | p.Ile582Thr | missense_variant | 10/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249302Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134952
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459536Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726188
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces isoleucine with threonine at codon 582 of the DICER1 protein (p.Ile582Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs749686370, ExAC 0.003%). This missense change has been observed in individual(s) with pleuropulmonary blastoma (PMID: 26925222). ClinVar contains an entry for this variant (Variation ID: 254293). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota | Nov 10, 2014 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research | Jul 01, 2019 | ACMG criteria met: PP4, BP1 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at