Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000020.3(ACVRL1):c.1217G>A (p.Trp406Ter)

CA16614169

411300 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d987cba8-4ecb-425f-82d1-133e39a24e1f

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_000020.3:c.1217G>A

NM_000020.3(ACVRL1):c.1217G>A (p.Trp406Ter)

NC_000012.12:g.51916204G>A

CM000674.2:g.51916204G>A

NC_000012.11:g.52309988G>A

CM000674.1:g.52309988G>A

NC_000012.10:g.50596255G>A

NG_009549.1:g.13787G>A

ENST00000547400.6:c.947G>A

ENST00000551576.6:c.1217G>A

ENST00000552678.2:c.1217G>A

ENST00000388922.9:c.1217G>A

ENST00000388922.8:c.1217G>A

ENST00000419526.6:c.695G>A

ENST00000547632.1:n.492G>A

ENST00000550683.5:c.1259G>A

ENST00000552678.1:c.222G>A

NM_000020.2:c.1217G>A

NM_001077401.1:c.1217G>A

NM_001077401.2:c.1217G>A

Pathogenic

PVS1 PS4_Supporting PM2_Supporting

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 ACVRL1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Hemorrhagic Telangiectasia VCEP

The NM_000020.3: c.1217G>A (p.Trp406Ter) variant in ACVRL1 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 8 (out of 10) leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in a proband with a phenotype consistent of HHT (PS4_Supporting; Internal lab contributors). In summary, this variant meets the criteria to be classified as pathogenic 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: PVS1, PM2_Supporting, PS4_Supporting (specification version 1.0.0; 1/4/2024).

PVS1

PS4_Supporting

This variant has been reported in a proband with a phenotype consistent of HHT (PS4_Supporting; Internal lab contributors).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

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