Submissions for variant NM_001033855.3(DCLRE1C):c.728A>G (p.His243Arg)

gnomAD frequency: 0.14770  dbSNP: rs12768894

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV001510060	SCV005375435	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2024-01-23	reviewed by expert panel	curation	The c.728A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Histidine by Arginine at amino acid 243 (p.His243Arg). The filtering allele frequency (the lower threshold of the 95% CI of 13221/60002) of the c.728A>G variant in DCLRE1C is 0.2249 for Admixed American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, 23214 adult homozygous have been reported (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency, based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 and BS2_Supporting (VCEP specifications version 1).
PreventionGenetics, part of Exact Sciences	RCV000253217	SCV000305991	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307635	SCV000361557	benign	Histiocytic medullary reticulosis	2018-01-13	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000253217	SCV000538774	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Labcorp Genetics (formerly Invitae), Labcorp	RCV001510060	SCV001716996	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001510060	SCV001750446	benign	Severe combined immunodeficiency due to DCLRE1C deficiency	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001723845	SCV001950534	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000253217	SCV004233967	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV001723845	SCV005316847	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000307635	SCV001455083	benign	Histiocytic medullary reticulosis	2020-09-16	no assertion criteria provided	clinical testing