Submissions for variant NM_024782.3(NHEJ1):c.530-2A>T

dbSNP: rs1064793763

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486247	SCV000566969	pathogenic	not provided	2017-07-10	criteria provided, single submitter	clinical testing	The c.530-2A>T variant in the NHEJ1 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 4. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product ifthe message is used for protein translation. The c.530-2A>T variant was not observed in approximately6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. We interpret c.530-2A>T as a pathogenic variant.
3billion, Medical Genetics	RCV002283483	SCV002572686	pathogenic	Cernunnos-XLF deficiency	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site is predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with NHEJ1-related disorder (ClinVar ID: VCV000419273 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.