rs878855239
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP7
This summary comes from the ClinGen Evidence Repository: The NM_177438.3:c.1089C>T (p.Phe363=) variant is a synonymous (silent) variant that is not predicted to impact splicing by MaxEntScan or SpliceAI (BP4, BP7). The total allele frequency in gnomAD v4.1.0 is 0.000001368 (2/1461842 alleles) with a highest population minor allele frequency of 0.00003312 (2/60394 alleles) in a population of undisclosed ancestry (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1.3.0; 04/23/2024) LINK:https://erepo.genome.network/evrepo/ui/classification/CA10583223/MONDO:0100216/024
Frequency
Consequence
NM_177438.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.1089C>T | p.Phe363= | synonymous_variant | 8/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.1089C>T | p.Phe363= | synonymous_variant | 8/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461842Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727214
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen | Apr 23, 2024 | The NM_177438.3:c.1089C>T (p.Phe363=) variant is a synonymous (silent) variant that is not predicted to impact splicing by MaxEntScan or SpliceAI (BP4, BP7). The total allele frequency in gnomAD v4.1.0 is 0.000001368 (2/1461842 alleles) with a highest population minor allele frequency of 0.00003312 (2/60394 alleles) in a population of undisclosed ancestry (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1.3.0; 04/23/2024) - |
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at