rs773875981
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_177438.3(DICER1):c.5528-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_177438.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250834Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135782
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727202
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:1
The DICER1 c.5528-6T>C variant has not been reported in individuals with DICER1-related conditions in the published literature. The frequency of this variant in the general population, 0.000008 (2/250834 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on DICER1 mRNA splicing yielded inconclusive findings. Based on the available information, we are unable to determine the clinical significance of this variant. -
Hereditary cancer-predisposing syndrome Uncertain:1
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DICER1-related tumor predisposition Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at