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_001114753.3(ENG):c.-9G>A

CA5253269

414302 (ClinVar)

Gene: ENG

Condition: telangiectasia, hereditary hemorrhagic, type 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9d79f81b-6d66-4029-a41e-15502e010aaa

HGVS expressions

NM_001114753.3:c.-9G>A

NM_001114753.3(ENG):c.-9G>A

NC_000009.12:g.127854364C>T

CM000671.2:g.127854364C>T

NC_000009.11:g.130616643C>T

CM000671.1:g.130616643C>T

NC_000009.10:g.129656464C>T

NG_009551.1:g.5405G>A

ENST00000373203.9:c.-9G>A

ENST00000344849.4:c.-9G>A

ENST00000373203.8:c.-9G>A

NM_000118.3:c.-9G>A

NM_001114753.2:c.-9G>A

Uncertain Significance

PS3_Supporting BP5

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 ENG Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Hemorrhagic Telangiectasia VCEP

The NM_001114753.3: c.-9G>A variant is located in the 5' UTR of ENG. Because the variant is located in the 5' UTR, is it not expected to alter the amino acid sequence. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0007942 (76/95698 alleles) in the European (non-Finnish) population. This variant has been observed in patients with an alternate molecular basis for disease (patients also carry a likely pathogenic/pathogenic ACVRL1 variant) (BP5; Internal lab contributors). Expression studies showed this variant causes a small reduction (~18.4%) of endoglin compared to wild type (PS3_Supporting, PMID: 22192717). Due to conflicting evidence, this variant is 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: PS3_Supporting, BP5 (specification version 1.0.0; 1/4/2024).

PS3_Supporting

Expression studies showed this variant causes a small reduction (~18.4%) of endoglin compared to wild type (PS3_Supporting, PMID: 22192717).

BP5

This variant has been observed in patients with an alternate molecular basis for disease (also carriers likely pathogenic/pathogenic ACVRL1 variant) (BP5; Internal lab contributors).

PM2

The highest population minor allele frequency in gnomAD v2.1.1 is 0.0007942 (76/95698 alleles) in the European (non-Finnish) population.

Approved on: 2024-03-15

Published on: 2024-03-15

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