Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_006321.4(ARIH2):c.1411-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely pathogenic (no stars).
ARIH2 (HGNC:690): (ariadne RBR E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin-protein ligase that polyubiquitinates some proteins, tagging them for degradation. The encoded protein upregulates p53 in some cancer cells and may inhibit myelopoiesis. Several transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been determined yet. [provided by RefSeq, Nov 2015]
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-48983196-C-T is Pathogenic according to our data. Variant chr3-48983196-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2692232.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42). . Strength limited to SUPPORTING due to the PP5.