Submissions for variant NM_001122955.4(BSCL2):c.845C>T (p.Ala282Val)

gnomAD frequency: 0.00096  dbSNP: rs185341934

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000401336	SCV000372877	benign	Congenital generalized lipodystrophy type 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000301053	SCV000372878	benign	Neuronopathy, distal hereditary motor, type 5A	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000431177	SCV000511349	likely benign	not provided	2017-09-06	criteria provided, single submitter	clinical testing
Invitae	RCV001083807	SCV000562700	benign	Charcot-Marie-Tooth disease type 2	2024-01-27	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000518650	SCV000612496	benign	not specified	2017-05-24	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174402	SCV001337540	likely benign	Monogenic diabetes	2017-01-02	criteria provided, single submitter	research	ACMG criteria: PP3 (9 predictors), BS2 (3 homozygotes in Latinos), BP6 (InVitae and Athena call it benign)=Likely benign
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000431177	SCV001474174	benign	not provided	2022-06-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000431177	SCV001939434	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000431177	SCV002544570	likely benign	not provided	2022-04-01	criteria provided, single submitter	clinical testing	BSCL2: PP3, BS1
Ambry Genetics	RCV002365351	SCV002660193	likely benign	Inborn genetic diseases	2022-04-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV000401336	SCV004698135	uncertain risk allele	Congenital generalized lipodystrophy type 2		criteria provided, single submitter	research	Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role of this particular variant rs185341934 of Congenital Generalized Lipodystrophy type 2 remains uncertain
PreventionGenetics, part of Exact Sciences	RCV003940156	SCV004756248	benign	BSCL2-related disorder	2019-07-30	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).