Submissions for variant NM_001110556.2(FLNA):c.7756+8A>G

gnomAD frequency: 0.00057  dbSNP: rs201663443

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153247	SCV000202721	likely benign	not specified	2014-04-09	criteria provided, single submitter	clinical testing
Invitae	RCV000234543	SCV000287156	benign	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2024-01-20	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659677	SCV000781520	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001573652	SCV001841276	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001573652	SCV002049983	benign	not provided	2023-10-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002505163	SCV002797200	benign	Cardiac valvular dysplasia, X-linked; FG syndrome 2; Heterotopia, periventricular, X-linked dominant; Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked; Melnick-Needles syndrome; Oto-palato-digital syndrome, type I; Oto-palato-digital syndrome, type II; Terminal osseous dysplasia-pigmentary defects syndrome; Frontometaphyseal dysplasia 1	2022-03-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000153247	SCV004223369	benign	not specified	2023-11-06	criteria provided, single submitter	clinical testing	Variant summary: FLNA c.7756+8A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00053 in 180346 control chromosomes. The observed variant frequency is approximately 1703-fold of the estimated maximal expected allele frequency for a pathogenic variant in FLNA causing Periventricular Nodular Heterotopia phenotype (3.1e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.7756+8A>G in individuals affected with Periventricular Nodular Heterotopia and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573652	SCV001799849	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001573652	SCV001809571	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001573652	SCV001930068	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573652	SCV001966607	likely benign	not provided		no assertion criteria provided	clinical testing