Submissions for variant NM_001033855.3(DCLRE1C):c.959C>G (p.Ser320Cys)

gnomAD frequency: 0.01123  dbSNP: rs41298896

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV001083680	SCV004102780	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2023-11-14	reviewed by expert panel	curation	The NM_001033855.3:c.959C>G variant in DCLRE1C is a missense variant predicted to cause substitution of serine by cysteine at amino acid 320 (p.Ser320Cys). This variant has an allele frequency of 0.03553 in the African / African American population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, 16 adult homozygous individuals with this variant are present in gnomAD v2.1.1 (in African/African American population)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
GeneDx	RCV000124664	SCV000168097	benign	not provided	2018-12-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26915675)
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre	RCV000124664	SCV000221370	likely pathogenic	not provided		criteria provided, single submitter	research
Illumina Laboratory Services, Illumina	RCV000348357	SCV000361552	benign	Histiocytic medullary reticulosis	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV001083680	SCV000645230	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000124664	SCV001473590	benign	not provided	2020-08-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000124664	SCV004126478	benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	DCLRE1C: BS1, BS2
Natera, Inc.	RCV001831916	SCV002082295	likely benign	Athabaskan severe combined immunodeficiency	2019-11-12	no assertion criteria provided	clinical testing