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]
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  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • There was no gene found in the curated document received from the VCI/VCEP
  • Gene listed was thus derived from ClinVar and/or CAR
  • See Evidence submitted by expert panel for details.

Variant: NC_012920.1:m.5293G>A

CA414779707

692567 (ClinVar)

Gene: MT-ND2
Condition: mitochondrial disease
Inheritance Mode: Mitochondrial inheritance
Link to MONDO
UUID: 79eb99b0-f488-4d4a-b8fb-8484ec1f77af

HGVS expressions

NC_012920.1:m.5293G>A
J01415.2:m.5293G>A
ENST00000361453.3:n.824G>A

Likely Benign

Met criteria codes 2
BP4 BP2
Not Met criteria codes 2
BS2 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The m.5293G>A (p.S275N) variant in MT-ND2 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is present in 1/49,487 sequences (1/509 in H1c) in Genbank per MITOMAP queried 10/29/2019. This variant is seen at homoplasmy in a proband, healthy brother, and healthy mother (PMID: 23813926). The proband had a pathogenic mtDNA variant, m.14487T>C, present at high heteroplasmy levels (BP2). The proband was particularly severe having Leigh syndrome at 6 months old however the m.5293G>A variant is homoplasmic in all family members including healthy individuals. Of note, this family is haplogroup H1 as is report in GenBank sequences. Additionally, the computational predictor APOGEE gives a consensus rating of neutral with a low pathogenicity predictor score, 0.46 (Min=0, Max=1), evidence that does not predict a damaging effect on gene function (BP4). In summary, this variant meets criteria to be classified as likely benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP2, BP4.
Met criteria codes
BP4
The computational predictor APOGEE gives a consensus rating of neutral with a low pathogenicity predictor score, 0.46 (Min=0, Max=1), evidence that does not predict a damaging effect on gene function (BP4).
BP2
This variant is seen at homoplasmy in proband, healthy brother, and healthy mother (PMID: 23813926). The proband had a pathogenic mtDNA variant, m.14487T>C, present at high heteroplasmy levels.
Not Met criteria codes
BS2
This variant is seen at homoplasmy in proband, healthy brother, and healthy mother (PMID: 23813926). The proband had a pathogenic mtDNA variant, m.14487T>C, present at high heteroplasmy levels. The proband was particularly severe having Leigh syndrome at 6 months old however the m.5293G>A variant is homoplasmic in all family members including healthy individuals. Of note, this family is haplogroup H1 as is report in GenBank sequences.
PM2
Present in 1/49,487 sequences (1/509 in H1c) in Genbank per MITOMAP queried 10/29/2019.
Approved on: 2022-03-24
Published on: 2022-03-24
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