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]

Variant: NM_000020.3(ACVRL1):c.137G>C (p.Cys46Ser)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA384897664

533345 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e12475b5-168e-4263-8406-f945e2847af9

Approved on: 2024-01-04

Published on: 2025-03-02

HGVS expressions

NM_000020.3:c.137G>C

NM_000020.3(ACVRL1):c.137G>C (p.Cys46Ser)

NC_000012.12:g.51913174G>C

CM000674.2:g.51913174G>C

NC_000012.11:g.52306958G>C

CM000674.1:g.52306958G>C

NC_000012.10:g.50593225G>C

NG_009549.1:g.10757G>C

ENST00000547400.6:c.179G>C

ENST00000551576.6:c.137G>C

ENST00000552678.2:c.137G>C

ENST00000388922.9:c.137G>C

ENST00000388922.8:c.137G>C

ENST00000419526.6:c.103+639G>C

ENST00000547400.5:c.179G>C

ENST00000550683.5:c.179G>C

ENST00000551576.5:c.137G>C

NM_000020.2:c.137G>C

NM_001077401.1:c.137G>C

NM_001077401.2:c.137G>C

Likely Pathogenic

PM2_Supporting PS4 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 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Hemorrhagic Telangiectasia VCEP

The NM_000020.3: c.137G>C variant in ACVRL1 is a missense variant predicted to cause substitution of cysteine by serine at amino acid 46 (p.Cys46Ser). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in 4 probands with a phenotype consistent with HHT (PS4; ClinVar, Internal lab contributors). The computational predictor REVEL gives a score of 0.852, 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 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: PS4, PM2_Supporting, PP3 (specification version 1.1.0; 1/4/2024).

PM2_Supporting

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

PS4

This variant has been reported in 4 probands with a phenotype consistent with HHT (PS4; ClinVar, Internal lab contributors).

PP3

The computational predictor REVEL gives a score of 0.852, which is above the threshold of ≥0.644, evidence that correlates with impact to ACVRL1 function (PP3).

Curation History

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