Submissions for variant NM_032737.4(LMNB2):c.704G>A (p.Arg235Gln)

gnomAD frequency: 0.01005  dbSNP: rs121912497

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551638	SCV000656065	benign	Progressive myoclonic epilepsy type 9; Lipodystrophy, partial, acquired, susceptibility to	2024-01-29	criteria provided, single submitter	clinical testing
Mendelics	RCV000990135	SCV001140952	benign	Progressive myoclonic epilepsy type 9	2019-05-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000057200	SCV001144437	benign	not provided	2018-12-12	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000015561	SCV001435271	likely benign	Acquired partial lipodystrophy		criteria provided, single submitter	research	The heterozygous p.Arg235Gln variant in LMNB2 has been identified in 2 individuals with acquired partial lipodystrophy (PMID: 16826530), but has also been identified in >1% of European (non-Finnish) chromosomes and 27 homozygotes by ExAC (http://gnomad.broadinstitute.org/). Acquired partial lipodistrophy is not known to be a Mendelian genetic disease. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for acquired partial lipodystrophy.
CeGaT Center for Human Genetics Tuebingen	RCV000057200	SCV002546036	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	LMNB2: BP4, BS1, BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224099	SCV003920152	likely benign	Progressive myoclonic epilepsy type 9; Lipodystrophy, partial, acquired, susceptibility to; Microcephaly 27, primary, autosomal dominant	2022-05-26	criteria provided, single submitter	clinical testing	This variant has been reported in the literature in at least 2 individuals with acquired partial lipodystrophy as well as 1 individual with familial partial lipodystrophy (Hegele 2006 PMID:16826530, Akinci 2017 PMID:28641778). This variant is present in the Genome Aggregation Database (Highest reported MAF 1.5% (160/10626) including 3 homozygotes (https://gnomad.broadinstitute.org/variant/19-2435152-C-T?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:14474). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000057200	SCV005207536	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000015561	SCV000035826	risk factor	Acquired partial lipodystrophy	2006-08-01	no assertion criteria provided	literature only
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057200	SCV000088313	not provided	not provided		no assertion provided	not provided
Genetic Services Laboratory, University of Chicago	RCV000117496	SCV000151714	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.