14-95090641-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP2PP3BP4BP6_StrongBS2
The NM_177438.3(DICER1):c.5626G>A(p.Gly1876Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★). Synonymous variant affecting the same amino acid position (i.e. G1876G) 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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DICER1 | NM_177438.3 | c.5626G>A | p.Gly1876Arg | missense_variant | 27/27 | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.5626G>A | p.Gly1876Arg | missense_variant | 27/27 | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251468Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135904
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727236
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152136Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74312
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | - - |
Uncertain significance, reviewed by expert panel | curation | ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen | Feb 03, 2023 | The NM_177438.2:c.5626G>A variant in DICER1 is a missense variant predicted to cause substitution of glycine by arginine at amino acid 1876 (p.Gly1876Arg). The highest population minor allele frequency in gnomAD v 2.1.1 is 0.0002772 (6/21648 alleles) in the European (Finnish) population followed by 0.00002891 (1/34592 alleles) in the Latino/Admixed American population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.41, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as Uncertain for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4. (Bayesian Points: -1; VCEP specifications version 1.1.0; 02/03/2023). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2022 | The p.G1876R variant (also known as c.5626G>A), located in coding exon 26 of the DICER1 gene, results from a G to A substitution at nucleotide position 5626. The glycine at codon 1876 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at