Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_177438.3(DICER1):c.904-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,603,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
Variant 14-95124672-CA-C is Benign according to our data. Variant chr14-95124672-CA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 417058.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Likely benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Jun 27, 2023
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
Mar 17, 2022
- -
DICER1-related tumor predisposition Benign:1
Likely benign, criteria provided, single submitter