Submissions for variant NM_001114753.3(ENG):c.572G>A (p.Gly191Asp)

gnomAD frequency: 0.01000  dbSNP: rs41322046

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel, ClinGen	RCV000205223	SCV004805875	benign	Telangiectasia, hereditary hemorrhagic, type 1	2024-03-15	reviewed by expert panel	curation	The NM_001114753.3: c.572G>A variant in ENG is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 191 (p.Gly191Asp). The filtering allele frequency (the lower threshold of the 95% CI of 1725/109328) of the c.572G>A variant in ENG is 0.01669 for European (non-Finnish) chromosomes by gnomAD v2.1.1, which is higher than the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel threshold (>0.01) for BA1, and therefore meets this criterion (BA1). This variant has been observed in at least 2 patients with an alternate molecular basis for disease (patients also carry likely pathogenic/pathogenic ACVRL1 variant) (BP5; PMID: 32573726, Internal lab contributors). The computational predictor REVEL gives a score of 0.275, which is neither above nor below the thresholds predicting a damaging or benign impact on ENG function. In summary, this variant meets the criteria to be classified as benign for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: BA1, BP5 (specification version 1.0.0; 1/4/2024).
GeneDx	RCV000200751	SCV000250070	benign	not specified	2016-04-25	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084372	SCV000261828	benign	Hereditary hemorrhagic telangiectasia	2024-02-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000200751	SCV000343678	benign	not specified	2016-07-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000205223	SCV000477345	likely benign	Telangiectasia, hereditary hemorrhagic, type 1	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000205223	SCV000603444	benign	Telangiectasia, hereditary hemorrhagic, type 1	2023-10-20	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000200751	SCV000712066	benign	not specified	2016-04-25	criteria provided, single submitter	clinical testing	Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: High frequency
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000205223	SCV001441141	likely benign	Telangiectasia, hereditary hemorrhagic, type 1	2018-01-01	criteria provided, single submitter	research	BS1 +BP2+BP6
CeGaT Center for Human Genetics Tuebingen	RCV001706172	SCV002546086	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ENG: BS1, BS2
Ambry Genetics	RCV002345702	SCV002648493	benign	Cardiovascular phenotype	2016-06-09	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.
Fulgent Genetics, Fulgent Genetics	RCV000205223	SCV002798100	likely benign	Telangiectasia, hereditary hemorrhagic, type 1	2022-02-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001706172	SCV005227524	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003891766	SCV000302343	benign	ENG-related disorder	2019-05-17	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000200751	SCV001743973	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000200751	SCV001807917	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000200751	SCV001925356	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001706172	SCV001929714	likely benign	not provided		no assertion criteria provided	clinical testing