Submissions for variant NM_004750.5(CRLF1):c.397+1G>A

dbSNP: rs137853932

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003231876	SCV003929999	likely pathogenic	not provided	2022-12-05	criteria provided, single submitter	clinical testing	Identified in an individual with CRLF1-related disorder, however segregation data and detailed clinical information were not provided (Piras et al., 2014); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24488861)
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV003236599	SCV003934967	likely pathogenic	Cone-rod dystrophy 12	2023-06-22	criteria provided, single submitter	clinical testing	The homozygous pathogenic variant c.397+1G>A has been identified in a proband with features of arthrogryposis multiple congenita, global developmental delay. Failure to thrive, bilateral CTEV and knee & finger contractures. This variant is identified in intron 2 of CRLF1 gene where loss of function is a reported mechanism with 18 pathogenic variants. This variant is predicted to cause exon 2 skipping with 10% loss of transcript however, it does not alter the reading frame. Hence, the ACMG criteria of PVS1_strong is met. The variant has not been identified yet in gnomAD database (PM2_moderate). It has been previously reported (PP5_supporting) PMID 31497877.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003988099	SCV004804924	pathogenic	Cold-induced sweating syndrome 1	2024-03-17	criteria provided, single submitter	research