chr14-95104062-T-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_177438.3(DICER1):āc.3334A>Gā(p.Asn1112Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. N1112N) 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 -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.3334A>G | p.Asn1112Asp | missense_variant | 21/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.3334A>G | p.Asn1112Asp | missense_variant | 21/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000718 AC: 18AN: 250782Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135708
GnomAD4 exome AF: 0.0000581 AC: 85AN: 1461810Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727202
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74460
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not specified Benign:1Other:1
Likely benign, criteria provided, single submitter | curation | Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research | Jul 01, 2019 | ACMG criteria met: BS1, BP1, BP4 - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 18, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 30093976, 26241669, 29762508) - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at