Submissions for variant NM_006767.4(LZTR1):c.2373C>T (p.His791=)

gnomAD frequency: 0.00299  dbSNP: rs148993324

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV004732485	SCV005367691	benign	RASopathy	2024-09-17	reviewed by expert panel	curation	The NM_006767.4:c.2373C>T (p.His791=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by UCSC Genome Browser (BP4, BP7). The highest population filtering allele frequency in gnomAD v4 is 0.009141 (730/75058 alleles) in African/African American population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1, BP4, BP7. (RASopathy VCEP specifications version 1.1; 9/17/2024)
GeneDx	RCV000873721	SCV000714260	likely benign	not provided	2021-09-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000873721	SCV001015773	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000604326	SCV001442732	benign	not specified	2020-10-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813516	SCV002060541	benign	Noonan syndrome and Noonan-related syndrome	2021-06-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002456320	SCV002736971	benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2018-12-04	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center	RCV000604326	SCV001919496	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000604326	SCV001955694	benign	not specified		no assertion criteria provided	clinical testing