Submissions for variant NM_006393.3(NEBL):c.2054C>T (p.Ala685Val)

gnomAD frequency: 0.00051  dbSNP: rs146218038

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000216150	SCV000270607	benign	not specified	2017-11-22	criteria provided, single submitter	clinical testing	p.Ala685Val in exon 20 of NEBL: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of note, orangutan, Chinese tree shrew, naked mole rat and rabbit have a valine (Va l) at this position despite high nearby amino acid conservation. In addition, co mputational prediction tools do not suggest a high likelihood of impact to the p rotein. In addition, this variant has been identified in 0.2% (55/25788) of Eur opean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broa dinstitute.org; dbSNP rs146218038). BA1, BP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV000862665	SCV001003200	likely benign	Primary dilated cardiomyopathy	2024-01-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001762460	SCV002008520	likely benign	not provided	2019-06-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004754358	SCV005348631	likely benign	NEBL-related disorder	2024-09-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).