Submissions for variant NM_001271208.2(NEB):c.9467T>A (p.Ile3156Asn) (rs145770770)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000224006	SCV000281035	benign	not provided	2015-12-21	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000242273	SCV000307408	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000242273	SCV000519843	benign	not specified	2016-03-03	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.
Athena Diagnostics Inc	RCV000242273	SCV000614186	likely benign	not specified	2017-05-23	criteria provided, single submitter	clinical testing
Invitae	RCV000557476	SCV000640898	benign	Nemaline myopathy 2	2020-12-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000242273	SCV001361229	benign	not specified	2019-04-22	criteria provided, single submitter	clinical testing	Variant summary: NEB c.9467T>A (p.Ile3156Asn) results in a non-conservative amino acid change in the encoded protein sequence. One of two in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 280432 control chromosomes, predominantly at a frequency of 0.021 within the South Asian subpopulation in the gnomAD database, including 8 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 6-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in NEB causing Nemaline Myopathy 2 phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.9467T>A in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000224006	SCV001800344	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000242273	SCV001929890	benign	not specified		no assertion criteria provided	clinical testing