Submissions for variant NM_006397.3(RNASEH2A):c.662A>G (p.Lys221Arg)

gnomAD frequency: 0.00038  dbSNP: rs143534021

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000625140	SCV000410828	likely benign	Aicardi-Goutieres syndrome 4	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625140	SCV000743854	likely benign	Aicardi-Goutieres syndrome 4	2014-12-07	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625140	SCV000745267	likely benign	Aicardi-Goutieres syndrome 4	2015-09-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000625140	SCV000761440	benign	Aicardi-Goutieres syndrome 4	2025-02-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001573855	SCV004137905	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	RNASEH2A: BP4
Breakthrough Genomics, Breakthrough Genomics	RCV001573855	SCV005209495	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573855	SCV001800305	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003922396	SCV004754485	likely benign	RNASEH2A-related disorder	2022-02-14	no assertion criteria provided	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).