Submissions for variant NM_001033855.3(DCLRE1C):c.1903dup (p.Ser635fs) (rs760288938)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000530013	SCV000645223	likely benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2019-12-31	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000779020	SCV000915464	uncertain significance	Histiocytic medullary reticulosis	2017-08-31	criteria provided, single submitter	clinical testing	The DCLRE1C c.1903dupA (p.Ser635LysfsTer6) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant has not therefore been reported in the literature in association with Omenn syndrome. The p.Ser635LysfsTer6 variant is reported at a frequency of 0.002465 in the Ashkenazi Jewish population from the Genome Aggregation Database. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Based on the potential impact of frameshift variants and the lack of clarifying evidence, the p.Ser635LysfsTer6 variant is classified as a variant of unknown significance but suspicious for pathogenicity for Omenn syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.