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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_014297.5(ETHE1):c.6G>A (p.Ala2=)

CA9487981

260385 (ClinVar)

Gene: ETHE1
Condition: ethylmalonic encephalopathy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 1931d802-2e7e-48dd-b06f-68f862cfb491
Approved on: 2021-05-07
Published on: 2021-05-07

HGVS expressions

NM_014297.5:c.6G>A
NM_014297.5(ETHE1):c.6G>A (p.Ala2=)
ENST00000292147.7:c.6G>A
ENST00000292147.6:c.6G>A
ENST00000458714.2:c.135+546C>T
ENST00000594342.5:c.6G>A
ENST00000595115.1:n.59G>A
ENST00000598330.1:c.6G>A
ENST00000600651.5:c.6G>A
ENST00000602138.1:c.6G>A
NM_014297.3:c.6G>A
NM_001320867.1:c.6G>A
NM_001320868.1:c.-215G>A
NM_001320869.1:c.6G>A
NM_014297.4:c.6G>A
NM_001320867.2:c.6G>A
NM_001320868.2:c.-215G>A
NM_001320869.2:c.6G>A
NC_000019.10:g.43527172C>T
CM000681.2:g.43527172C>T
NC_000019.9:g.44031324C>T
CM000681.1:g.44031324C>T
NC_000019.8:g.48723164C>T
NG_008141.1:g.5073G>A

Benign

Met criteria codes 3
BS2 BP7 BA1
Not Met criteria codes 4
BS1 PS1 PM5 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The allele frequency of the c.6G>A variant in the ETHE1 gene is reported as >16% in gnomAD, including >2,000 homozygotes, which is high enough to be classified as benign based on thresholds defined by the ClinGen ETHE1 Variant Curation Expert Panel (>0.1% in gnomAD- BA1 and BS2). In silico splicing predictors (Splice AI) do not predict a deleterious effect (BP7). In summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1-specific ACMG/AMP criteria applied: (BA1, BS2, BP7).
Met criteria codes
BS2
Allele frequency is reported as >16% in gnomAD, including >2,000 homozygotes
BP7
This is a synonymous change that is not predicted to affect splicing. Splice AI score is 0.0 for acceptor loss and gain and 0.0 for donor loss and gain
BA1
Allele frequency is reported as >16% in gnomAD, including >2,000 homozygotes, which is higher than the cutoff proposed for ETHE1 variants at >0.1%
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Multiple individuals are homozygotes for this mutation in ExAC
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.