Submissions for variant NM_015474.4(SAMHD1):c.626-1G>C

dbSNP: rs2146127849

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002013399	SCV002288367	likely pathogenic	Aicardi-Goutieres syndrome 5	2024-01-02	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 5 of the SAMHD1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of Aicardi-Goutieres syndrome (PMID: 24989684). ClinVar contains an entry for this variant (Variation ID: 1500266). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 24989684). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV003886546	SCV004704342	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	SAMHD1: PVS1, PM2, PM3:Supporting, PS3:Supporting
Fulgent Genetics, Fulgent Genetics	RCV005025623	SCV005661838	pathogenic	Aicardi-Goutieres syndrome 5; Chilblain lupus 2	2024-03-09	criteria provided, single submitter	clinical testing