rs545392797
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_177438.3(DICER1):c.4894T>C(p.Ser1632Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1632S) has been classified as Likely benign.
Frequency
Consequence
NM_177438.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.4894T>C | p.Ser1632Pro | missense_variant | 23/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.4894T>C | p.Ser1632Pro | missense_variant | 23/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251380Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135850
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727246
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74500
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 05, 2022 | - - |
Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 24, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 18, 2023 | - - |
DICER1-related tumor predisposition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at