rs875989781
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_177438.3(DICER1):c.4633_4634insT(p.Ser1545PhefsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S1545S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_177438.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4633_4634insT | p.Ser1545PhefsTer7 | frameshift_variant | 23/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4633_4634insT | p.Ser1545PhefsTer7 | frameshift_variant | 23/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Pathogenic:2
Pathogenic, criteria provided, single submitter | curation | Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research | Jul 01, 2019 | ACMG criteria met: PVS1, PM2, PP4 - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DICER1 are known to be pathogenic (PMID: 19556464, 21266384). This variant has been observed in individuals affected with DICER1 syndrome (PMID: 25022261, 28960912). ClinVar contains an entry for this variant (Variation ID: 225885). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser1545Phefs*7) in the DICER1 gene. It is expected to result in an absent or disrupted protein product. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 24, 2016 | - - |
Pineoblastoma Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Jul 15, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at