Submissions for variant NM_024570.4(RNASEH2B):c.2T>C (p.Met1Thr)

dbSNP: rs1457494794

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000819510	SCV000960174	uncertain significance	Aicardi-Goutieres syndrome 2	2021-09-01	criteria provided, single submitter	clinical testing	This sequence change affects the initiator methionine of the RNASEH2B mRNA. The next in-frame methionine is located at codon 31. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. Disruption of the initiator codon has been observed in individual(s) with clinical features of RNASEH2B-related conditions (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill	RCV000819510	SCV001251493	likely pathogenic	Aicardi-Goutieres syndrome 2		criteria provided, single submitter	research	The RNASEH2B c.2T>C (p.M1T) variant is predicted to result in the loss of a start codon corresponding to the first amino acid of the RNASEH2B protein, which may lead to an aberrant protein.