Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001348451.2(CHD1L):c.-78C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000235 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.139C>T (p.R47C) alteration is located in exon 2 (coding exon 2) of the CHD1L gene. This alteration results from a C to T substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -