Submissions for variant NM_001330078.2(NRXN1):c.772+1078A>G

gnomAD frequency: 0.00153  dbSNP: rs144049982

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153604	SCV000203147	likely benign	not specified	2015-05-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001704115	SCV000241846	likely benign	not provided	2021-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000467253	SCV000431212	likely benign	Pitt-Hopkins-like 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000467253	SCV000562380	likely benign	Pitt-Hopkins-like syndrome 2	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316971	SCV000850190	uncertain significance	Inborn genetic diseases	2018-08-14	criteria provided, single submitter	clinical testing	The p.D273G variant (also known as c.818A>G), located in coding exon 2 of the NRXN1 gene, results from an A to G substitution at nucleotide position 818. The aspartic acid at codon 273 is replaced by glycine, an amino acid with similar properties. Based on data from gnomAD, the G allele has an overall frequency of approximately 0.05% (141/264288) total alleles studied. The highest observed frequency was 0.56% (129/23136) of African alleles. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV000467253	SCV001519733	uncertain significance	Pitt-Hopkins-like syndrome 2	2019-02-01	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].