ClinVar

Description

The c.3813_3815delGAA variant (also known as p.K1271del) is located in coding exon 15 of the NIPBL gene. This variant results from an in-frame GAA deletion at nucleotide positions 3813 to 3815. This results in the in-frame deletion of a lysine at codon 1271. In one study, this variant was identified in B-lymphoblastoid cell line from an individual with Cornelia de Lange syndrome (CdLS). This study also showed that the cell line with this variant had an increase in the formation of chromatid exchanges and chromatid breaks when exposed to x-rays in the G2 cell cycle phase, consistent with a defect in double strand break repair through homologous recombination (Vrouwe MG et al. Hum. Mol. Genet., 2007 Jun;16:1478-87). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6491 samples (12982 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be and by PolyPhen and SIFT in silico analyses, respectively. Based on the majority of available evidence to date, this variant is likely to be pathogenic.