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.917C>T (p.Ala306Val)

CA6573017

811065 (ClinVar)

Gene: ACVRL1

Condition: telangiectasia, hereditary hemorrhagic, type 2

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4416f4e6-3f7f-4e9f-baf3-5f76bbb00beb

Approved on: 2024-03-15

Published on: 2024-03-15

HGVS expressions

NM_000020.3:c.917C>T

NM_000020.3(ACVRL1):c.917C>T (p.Ala306Val)

NC_000012.12:g.51915369C>T

CM000674.2:g.51915369C>T

NC_000012.11:g.52309153C>T

CM000674.1:g.52309153C>T

NC_000012.10:g.50595420C>T

NG_009549.1:g.12952C>T

ENST00000547400.6:c.647C>T

ENST00000551576.6:c.917C>T

ENST00000552678.2:c.917C>T

ENST00000388922.9:c.917C>T

ENST00000388922.8:c.917C>T

ENST00000419526.6:c.395C>T

ENST00000550683.5:c.959C>T

NM_000020.2:c.917C>T

NM_001077401.1:c.917C>T

NM_001077401.2:c.917C>T

Uncertain Significance

PP3 PM2

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.917C>T variant in ACVRL1 is a missense variant predicted to cause substitution of alanine by valine at amino acid 306 (p.Ala306Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001086 (14/128884 alleles) in the European (non-Finnish) population. The computational predictor REVEL gives a score of 0.365, 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: None (specification version 1.0.0; 1/4/2024).

PP3

The computational predictor REVEL gives a score of 0.365, which is neither above nor below the thresholds predicting a damaging or benign impact on ACVRL1 function.

PM2

The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001086 (14/128884 alleles) in the European (non-Finnish) population.

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