Submissions for variant NM_001033855.3(DCLRE1C):c.1791C>T (p.Cys597=)

gnomAD frequency: 0.00051  dbSNP: rs115421695

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV000950965	SCV004102785	likely benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2023-11-14	reviewed by expert panel	curation	The c.1791C>T (NM_001033855.3) variant in the DCLRE1C gene is a synonymous variant (p.Cys597=). The filtering allele frequency (the lower threshold of the 95% CI of 49/24970) of the c.1791C>T variant in DCLRE1C is 0.001381 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold 0.00078 for BS1, and therefore meets this criterion (BS1). Additionally, According to at least two in silico tools (SpliceAI and varSEAK) this synonymous variant was predicted not to impact the splice consensus sequence nor create a new splice site (BP7 met). A comprehensive literature search has not found the variant in individuals with SCID due to DCLRE1C deficiency. In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, BS1 and BP7, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
Invitae	RCV000950965	SCV001097310	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003960621	SCV004767617	likely benign	DCLRE1C-related disorder	2019-12-16	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).