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.113G>A (p.Ser38Asn)

CA384897562

1948619 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 04b1a103-d0c3-4ee2-873b-737e83bd9ce1

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_000020.3:c.113G>A

NM_000020.3(ACVRL1):c.113G>A (p.Ser38Asn)

NC_000012.12:g.51913150G>A

CM000674.2:g.51913150G>A

NC_000012.11:g.52306934G>A

CM000674.1:g.52306934G>A

NC_000012.10:g.50593201G>A

NG_009549.1:g.10733G>A

ENST00000547400.6:c.155G>A

ENST00000551576.6:c.113G>A

ENST00000552678.2:c.113G>A

ENST00000388922.9:c.113G>A

ENST00000388922.8:c.113G>A

ENST00000419526.6:c.103+615G>A

ENST00000547400.5:c.155G>A

ENST00000550683.5:c.155G>A

ENST00000551576.5:c.113G>A

NM_000020.2:c.113G>A

NM_001077401.1:c.113G>A

NM_001077401.2:c.113G>A

Uncertain Significance

PM2_Supporting

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 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.113G>A variant in ACVRL1 is a missense variant predicted to cause substitution of serine by asparagine at amino acid 38 (p.Ser38Asn). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00002814 (3/106620 alleles) in European (non-Finnish) population, which is lower than the ClinGen Hereditary Hemorrhagic Telangiectasia VCEP threshold (<0.00004, or <6 total alleles) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.321, which is neither above nor below the thresholds predicting a damaging or benign impact on ACVRL1 function. In summary, this variant meets the criteria to be classified as a variant of uncertain significance 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: PM2_Supporting (specification version 1.0.0; 1/04/2024).

PM2_Supporting

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00002814 (3/106620 alleles) in European (non-Finnish) population, which is lower than the ClinGen Hereditary Hemorrhagic Telangiectasia VCEP threshold (<0.00004, or <6 total alleles) for PM2_Supporting, meeting this criterion (PM2_Supporting).

PP3

The computational predictor REVEL gives a score of 0.321, which is neither above nor below the thresholds predicting a damaging or benign impact on ACVRL1 function.

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