Submissions for variant NM_133433.4(NIPBL):c.2447G>A (p.Arg816His)

gnomAD frequency: 0.00028  dbSNP: rs80358359

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723636	SCV000114525	uncertain significance	not provided	2013-04-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000146544	SCV000193839	likely benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000146544	SCV000491758	likely benign	not specified	2017-01-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV001155803	SCV001317266	likely benign	Cornelia de Lange syndrome 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000723636	SCV001371492	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NIPBL: BS1
Genome-Nilou Lab	RCV001155803	SCV002054179	likely benign	Cornelia de Lange syndrome 1	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426647	SCV002731526	uncertain significance	Inborn genetic diseases	2017-11-02	criteria provided, single submitter	clinical testing	The p.R816H variant (also known as c.2447G>A), located in coding exon 9 of the NIPBL gene, results from a G to A substitution at nucleotide position 2447. The arginine at codon 816 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV001155803	SCV003781886	benign	Cornelia de Lange syndrome 1	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945029	SCV004762945	benign	NIPBL-related condition	2020-09-28	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).