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]

Link to SEPIO compliant JSON-LD document

Variant: NM_014297.5(ETHE1):c.505+264T>G

CA14745070

671157 (ClinVar)

Gene: ETHE1

Condition: ethylmalonic encephalopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 143ae689-3954-4475-9e6d-de60097d722e

HGVS expressions

NM_014297.5:c.505+264T>G

NM_014297.5(ETHE1):c.505+264T>G

ENST00000292147.7:c.505+264T>G

ENST00000292147.6:c.505+264T>G

ENST00000594342.5:c.*68+264T>G

ENST00000598330.1:c.*68+264T>G

ENST00000600651.5:c.505+264T>G

NM_014297.3:c.505+264T>G

NM_001320867.1:c.472+264T>G

NM_001320868.1:c.136+264T>G

NM_001320869.1:c.211+264T>G

NM_014297.4:c.505+264T>G

NM_001320867.2:c.472+264T>G

NM_001320868.2:c.136+264T>G

NM_001320869.2:c.211+264T>G

NC_000019.10:g.43511173A>C

CM000681.2:g.43511173A>C

NC_000019.9:g.44015325A>C

CM000681.1:g.44015325A>C

NC_000019.8:g.48707165A>C

NG_008141.1:g.21072T>G

Benign

BS2 BA1

PM2

Evidence Links 0

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The c.505+264T>G (NM_014297.5) variant in ETHE1 is an intronic variant which is located in intron 4 (intron 4/6). The highest population minor allele frequency for the c.505+264T>G variant in gnomAD v2.1.1 is 0.077 (2,431/31,374 alleles) in the general population, which is higher than the ClinGen ETHE1 threshold >0.001 for BA1, and therefore meets this criterion (BA1). This variant has been observed in at least 169 homozygous individuals (gnomAD v2.1.1) with no features of ethylmalonic aciduria, petechiae, chronic diarrhea, acrocyanosis, nor developmental delay. In summary, this variant meets the criteria to be classified as benign, and therefore not causative of Autosomal Recessive Ethylmalonic Encephalopathy. ACMG/AMP criteria applied, as specified by the ClinGen ETHE1 VCEP (version 1.0): BA1, BS2. Approved 7/6/2021.

BS2

Seen in 169 homozygotes in gnomAD

BA1

Seen in over 2,400 alleles. AF is 0.07748 which exceeds VCEP threshold >0.001, including 169 homozygotes in gnomAD 6/24/2021

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2021-07-27

Published on: 2021-07-27

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