Submissions for variant NM_207361.6(FREM2):c.5434G>A (p.Ala1812Thr)

dbSNP: rs749830746

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000267681	SCV000384204	uncertain significance	Fraser syndrome 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001573735	SCV001986483	uncertain significance	not provided	2019-10-14	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003165838	SCV003862602	uncertain significance	Inborn genetic diseases	2023-02-06	criteria provided, single submitter	clinical testing	The c.5434G>A (p.A1812T) alteration is located in exon 4 (coding exon 4) of the FREM2 gene. This alteration results from a G to A substitution at nucleotide position 5434, causing the alanine (A) at amino acid position 1812 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573735	SCV001800036	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573735	SCV001969224	uncertain significance	not provided		no assertion criteria provided	clinical testing