rs377667473
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_177438.2:c.2651-4T>G variant in DICER1 is an intronic variant resulting from a T to G substitution 4 nucleotides upstream from coding exon 17. It is not predicted by MaxEntScan or SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved, as the variant is the reference nucleotide in more than 3 mammalian species in the UCSC Genome Browser Multiz Alignments track (BP4, BP7). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1; 02/11/2022) LINK:https://erepo.genome.network/evrepo/ui/classification/CA7331198/MONDO:0017288/024
Frequency
Consequence
NM_177438.3 splice_region, splice_polypyrimidine_tract, intron
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.2651-4T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000343455.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DICER1 | ENST00000343455.8 | c.2651-4T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_177438.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250392Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135548
GnomAD4 exome AF: 0.00000965 AC: 14AN: 1450844Hom.: 0 Cov.: 40 AF XY: 0.00000831 AC XY: 6AN XY: 722250
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
DICER1-related tumor predisposition Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2023 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen DICER1 and miRNA-Processing Gene Variant Curation Expert Panel, ClinGen | May 18, 2022 | The NM_177438.2:c.2651-4T>G variant in DICER1 is an intronic variant resulting from a T to G substitution 4 nucleotides upstream from coding exon 17. It is not predicted by MaxEntScan or SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved, as the variant is the reference nucleotide in more than 3 mammalian species in the UCSC Genome Browser Multiz Alignments track (BP4, BP7). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1; 02/11/2022) - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2021 | 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