Submissions for variant NM_001110556.2(FLNA):c.7903G>A (p.Glu2635Lys)

gnomAD frequency: 0.00010  dbSNP: rs369717556

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000866800	SCV001007942	likely benign	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2023-08-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001553477	SCV001774354	uncertain significance	not provided	2024-05-29	criteria provided, single submitter	clinical testing	Has not been published in a peer-reviewed journal to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
CeGaT Center for Human Genetics Tuebingen	RCV001553477	SCV002498188	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	FLNA: BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV001553477	SCV004225690	uncertain significance	not provided	2022-03-01	criteria provided, single submitter	clinical testing	PP2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987436	SCV004803254	likely benign	not specified	2024-01-02	criteria provided, single submitter	clinical testing	Variant summary: FLNA c.7903G>A (p.Glu2635Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.9e-05 in 1208917 control chromosomes, predominantly at a frequency of 8.1e-05 within the Non-Finnish European subpopulation in the gnomAD database including 22 hemizygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 260 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.7903G>A in individuals affected with Periventricular Nodular Heterotopia and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as likely benign (n=2) and VUS (n=1)Based on the evidence outlined above, the variant was classified as likely benign.
Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire	RCV000201336	SCV000239935	benign	Abnormality of neuronal migration	2014-10-31	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001553477	SCV001808629	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001553477	SCV001970672	uncertain significance	not provided		no assertion criteria provided	clinical testing