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.1377+4A>T

CA1139662707

994236 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 06132883-41d1-40e5-bc3c-9ec5c483cd79

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_000020.3:c.1377+4A>T

NM_000020.3(ACVRL1):c.1377+4A>T

NC_000012.12:g.51919119A>T

CM000674.2:g.51919119A>T

NC_000012.11:g.52312903A>T

CM000674.1:g.52312903A>T

NC_000012.10:g.50599170A>T

NG_009549.1:g.16702A>T

ENST00000547400.6:c.1107+4A>T

ENST00000551576.6:c.1377+4A>T

ENST00000552678.2:c.1381A>T

ENST00000388922.9:c.1377+4A>T

ENST00000388922.8:c.1377+4A>T

ENST00000419526.6:c.855+4A>T

ENST00000547632.1:n.656A>T

ENST00000550683.5:c.1419+4A>T

ENST00000552678.1:c.386A>T

NM_000020.2:c.1377+4A>T

NM_001077401.1:c.1377+4A>T

NM_001077401.2:c.1377+4A>T

Uncertain Significance

PP3 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.1377+4A>T variant in ACVRL1 is an intronic variant located in intron 9. 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). The computational splicing predictor SpliceAI gives a score of 0.39 for donor loss, predicting that the variant disrupts the donor splice site of intron 9 of ACVRL1 (PP3). 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, PS4_Supporting, PP3 (specification version 1.0.0; 1/04/2024).

PP3

The computational splicing predictor SpliceAI gives a score of 0.39 for donor loss, predicting that the variant disrupts the donor splice site of intron 9 of ACVRL1 (PP3).

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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