Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001114753.3(ENG):c.1762G>A (p.Val588Ile)

CA5252632

237024 (ClinVar)

Gene: ENG
Condition: telangiectasia, hereditary hemorrhagic, type 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a0ff594f-5659-4165-814c-872b4d962ef0
Approved on: 2024-09-11
Published on: 2024-09-19

HGVS expressions

NM_001114753.3:c.1762G>A
NM_001114753.3(ENG):c.1762G>A (p.Val588Ile)
NC_000009.12:g.127816033C>T
CM000671.2:g.127816033C>T
NC_000009.11:g.130578312C>T
CM000671.1:g.130578312C>T
NC_000009.10:g.129618133C>T
NG_009551.1:g.43736G>A
NG_023245.1:g.18159C>T
ENST00000480266.6:c.1216G>A
ENST00000373203.9:c.1762G>A
ENST00000344849.4:c.1762G>A
ENST00000373203.8:c.1762G>A
ENST00000480266.5:c.1216G>A
NM_000118.3:c.1762G>A
NM_001114753.2:c.1762G>A
NM_001278138.1:c.1216G>A
NM_001278138.2:c.1216G>A
More

Likely Benign

Met criteria codes 2
BP5 BP4
Not Met criteria codes 3
PM2 BA1 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Hemorrhagic Telangiectasia Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ENG Version 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hereditary Hemorrhagic Telangiectasia VCEP
The NM_001114753.3: c.1762G>A variant in ENG is a missense variant predicted to cause substitution of valine by isoleucine at amino acid 588 (p.Val588Ile). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0003436 (43/125140 alleles) in the non-Finnish European population. The computational predictor REVEL gives a score of 0.043, which is below the threshold of ≤0.1, and the splice site predictor SpliceAI indicated that the variant has no impact on splicing, evidence that does not predict a damaging effect on ENG function (BP4). This variant has been observed in a patient with an alternate molecular basis for disease (pathogenic variant identified in ACVRL1) (BP5; internal lab contributors). In summary, this variant meets the criteria to be classified as likely benign 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: BP4, BP5 (specifications version 1.1.0; 09/11/2024).
Met criteria codes
BP5
This variant has been observed in a patient with an alternate molecular basis for disease (pathogenic variant identified in ACVRL1) (BP5; internal lab contributors).
BP4
The computational predictor REVEL gives a score of 0.043, which is below the threshold of ≤0.1, and the splice site predictor SpliceAI indicated that the variant has no impact on splicing, evidence that does not predict a damaging effect on ENG function (BP4).
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0003436 (43/125140 alleles) in the non-Finnish European population.
Curation History
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