Submissions for variant NM_006005.3(WFS1):c.2141_2164del (p.Asn714_Asn721del)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003448859	SCV004176660	uncertain significance	Wolfram syndrome 1	2023-02-14	criteria provided, single submitter	clinical testing	The inframe deletion c.2141_2164del (p.Asn714_Asn721del) variant in WFS1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn714_Asn721del variant has allele frequency 0.0004% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This p.Asn714_Asn721del causes deletion of amino acid Asparagine at position 714 to Asparagine at position 721. This variant has not been reported to the ClinVar database. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Invitae	RCV003732589	SCV004536337	uncertain significance	not provided	2023-01-31	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with clinical features of autosomal recessive Wolfram syndrome (Invitae). This variant is present in population databases (rs771936108, gnomAD 0.003%). This variant, c.2141_2164del, results in the deletion of 8 amino acid(s) of the WFS1 protein (p.Asn714_Asn721del), but otherwise preserves the integrity of the reading frame.