Evidence Repository - Clinical Genome Resources

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Variant: NM_001114753.3(ENG):c.572G>A (p.Gly191Asp)

CA325327

213200 (ClinVar)

Gene: ENG

Condition: telangiectasia, hereditary hemorrhagic, type 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5e64b35b-3660-45cd-bc60-6e2be0e909ee

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_001114753.3:c.572G>A

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

NC_000009.12:g.127825812C>T

CM000671.2:g.127825812C>T

NC_000009.11:g.130588091C>T

CM000671.1:g.130588091C>T

NC_000009.10:g.129627912C>T

NG_009551.1:g.33957G>A

ENST00000480266.6:c.26G>A

ENST00000373203.9:c.572G>A

ENST00000344849.4:c.572G>A

ENST00000373203.8:c.572G>A

ENST00000462196.1:n.472G>A

ENST00000480266.5:c.26G>A

NM_000118.3:c.572G>A

NM_001114753.2:c.572G>A

NM_001278138.1:c.26G>A

NM_001278138.2:c.26G>A

Benign

BP5 BA1

PP3

Evidence Links 0

Expert Panel

Hereditary Hemorrhagic Telangiectasia VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Hemorrhagic Telangiectasia Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ENG Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Hemorrhagic Telangiectasia VCEP

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).

BP5

This variant has been observed in at least 2 patients with an alternate molecular basis for disease (patients also carry likely pathogenic/pathogenic ACVRL variant) (BP5; PMID: 32573726, Internal lab contributors).

BA1

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).

PP3

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.

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