Submissions for variant NM_000536.4(RAG2):c.1095T>C (p.Ser365=)

gnomAD frequency: 0.00139  dbSNP: rs140519815

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV003401297	SCV004102758	likely benign	Recombinase activating gene 2 deficiency	2023-11-14	reviewed by expert panel	curation	The NM_000536.4:c.1095T>C variant is a synonymous (silent) variant (p.Ser365=) with no predicted splice impact (BP7). This variant has not been reported in the literature in individuals with RAG2-related conditions. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00314 (79/25120) in the Finnish population, which is higher than the ClinGen SCID VCEP's threshold for BS1 (>0.00195). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive SCID based on the ACMG criteria applied BS1 and BP7, as specified by the ClinGen SCID VCEP (VCEP specifications 1).
Illumina Laboratory Services, Illumina	RCV000377795	SCV000371786	likely benign	Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000262415	SCV000371787	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000645689	SCV000767440	benign	Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001091956	SCV001248259	likely benign	not provided	2020-01-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001091956	SCV001470990	likely benign	not provided	2022-09-12	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000262415	SCV001457489	benign	Histiocytic medullary reticulosis	2020-04-13	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001091956	SCV001929485	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001091956	SCV001975706	likely benign	not provided		no assertion criteria provided	clinical testing