rs189119295
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_177438.3(DICER1):c.4819C>T(p.Arg1607Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4819C>T | p.Arg1607Trp | missense_variant | 23/27 | ENST00000343455.8 | NP_803187.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4819C>T | p.Arg1607Trp | missense_variant | 23/27 | 1 | NM_177438.3 | ENSP00000343745.3 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152140Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251372Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135844
GnomAD4 exome AF: 0.000134 AC: 196AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000114 AC XY: 83AN XY: 727248
GnomAD4 genome AF: 0.000164 AC: 25AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28748527) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 31, 2024 | The DICER1 c.4819C>T (p.Arg1607Trp) variant has been reported in the published literature in at least one individual with breast cancer (PMID: 33606809 (2021)). The frequency of this variant in the general population, 0.00048 (17/35436 chromosomes in Latino/Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. - |
DICER1-related tumor predisposition Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2022 | The c.4819C>T (p.R1607W) alteration is located in exon 23 (coding exon 22) of the DICER1 gene. This alteration results from a C to T substitution at nucleotide position 4819, causing the arginine (R) at amino acid position 1607 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at