Submissions for variant NM_001083116.3(PRF1):c.921del (p.His308fs)

gnomAD frequency: 0.00002  dbSNP: rs777345151

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centogene AG - the Rare Disease Company	RCV001250207	SCV001424476	likely pathogenic	Familial hemophagocytic lymphohistiocytosis 2		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001250207	SCV004519336	pathogenic	Familial hemophagocytic lymphohistiocytosis 2	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His308Thrfs*22) in the PRF1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 248 amino acid(s) of the PRF1 protein. This variant is present in population databases (rs777345151, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 32542393, 33746956). ClinVar contains an entry for this variant (Variation ID: 973565). This variant disrupts a region of the PRF1 protein in which other variant(s) (p.Asp491Asn) have been determined to be pathogenic (PMID: 24390453, 25577959, 33746956). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Lab, University of California San Francisco	RCV001250207	SCV004847156	pathogenic	Familial hemophagocytic lymphohistiocytosis 2	2023-06-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV004570639	SCV005052468	pathogenic	Aplastic anemia	2023-11-13	criteria provided, single submitter	clinical testing