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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000020.3(ACVRL1):c.652C>T (p.Arg218Trp)

CA6572962

802861 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7c22c73d-4f73-40b3-bf32-e0eb3a24a96b

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_000020.3:c.652C>T

NM_000020.3(ACVRL1):c.652C>T (p.Arg218Trp)

NC_000012.12:g.51914465C>T

CM000674.2:g.51914465C>T

NC_000012.11:g.52308249C>T

CM000674.1:g.52308249C>T

NC_000012.10:g.50594516C>T

NG_009549.1:g.12048C>T

ENST00000547400.6:c.382C>T

ENST00000551576.6:c.652C>T

ENST00000552678.2:c.652C>T

ENST00000388922.9:c.652C>T

ENST00000388922.8:c.652C>T

ENST00000419526.6:c.130C>T

ENST00000547400.5:c.382C>T

ENST00000550683.5:c.694C>T

NM_000020.2:c.652C>T

NM_001077401.1:c.652C>T

NM_001077401.2:c.652C>T

Likely Benign

PP3 BS1

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.652C>T variant in ACVRL1 is a missense variant predicted to cause substitution of arginine by tryptophan at amino acid 218 (p.Arg218Trp). The filtering allele frequency (the lower threshold of the 95% CI of 54/19950) of the c.652C>T variant in ACVRL1 is 0.002551 for East Asian chromosomes by gnomAD v2.1.1, which is higher than the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel threshold (>0.002) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.816, which is above the threshold of ≥0.644, evidence that correlates with impact to ACVRL1 function (PP3). In summary, this variant meets the criteria to be classified as likely 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: BS1, PP3 (specification version 1.0.0; 1/4/2024).

PP3

The computational predictor REVEL gives a score of 0.816, which is above the threshold of ≥0.644, evidence that correlates with impact to ACVRL1 function (PP3).

BS1

The filtering allele frequency (the lower threshold of the 95% CI of 54/19950) of the c.652C>T variant in ACVRL1 is 0.002551 for East Asian chromosomes by gnomAD v2.1.1, which is higher than the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel threshold (>0.002) for BS1, and therefore meets this criterion (BS1).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.