Submissions for variant NM_030962.3(SBF2):c.129G>A (p.Gln43=) (rs761285505)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV001094000	SCV000366474	uncertain significance	Charcot-Marie-Tooth disease, type 4B2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000432459	SCV000529626	likely benign	not specified	2016-07-07	criteria provided, single submitter	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.
Invitae	RCV000535477	SCV000657936	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-10-24	criteria provided, single submitter	clinical testing	This sequence change affects codon 43 of the SBF2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SBF2 protein. This variant is present in population databases (rs761285505, ExAC 0.006%) but has not been reported in the literature in individuals with an SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 301928). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.