Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_025265.4(TSEN2):c.910-179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 115,354 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
TSEN2 (HGNC:28422): (tRNA splicing endonuclease subunit 2) This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BP6
Variant 3-12516432-A-G is Benign according to our data. Variant chr3-12516432-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 677138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00453 (523/115354) while in subpopulation AFR AF= 0.0128 (433/33892). AF 95% confidence interval is 0.0118. There are 4 homozygotes in gnomad4. There are 254 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Review Status: criteria provided, single submitter
Collection Method: not provided
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Jun 14, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -