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NM_006796.3(AFG3L2):c.1875G>A (p.Met625Ile) AND Spinocerebellar ataxia type 28

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 3, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002265626.1

Allele description [Variation Report for NM_006796.3(AFG3L2):c.1875G>A (p.Met625Ile)]

NM_006796.3(AFG3L2):c.1875G>A (p.Met625Ile)

Gene:
AFG3L2:AFG3 like matrix AAA peptidase subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18p11.21
Genomic location:
Preferred name:
NM_006796.3(AFG3L2):c.1875G>A (p.Met625Ile)
Other names:
p.Met625Ile
HGVS:
  • NC_000018.10:g.12340306C>T
  • NG_023361.1:g.41971G>A
  • NM_006796.3:c.1875G>AMANE SELECT
  • NP_006787.2:p.Met625Ile
  • NP_006787.2:p.Met625Ile
  • LRG_666t1:c.1875G>A
  • LRG_666:g.41971G>A
  • LRG_666p1:p.Met625Ile
  • NC_000018.9:g.12340305C>T
  • NM_006796.2:c.1875G>A
Protein change:
M625I; MET625ILE
Links:
OMIM: 604581.0011; dbSNP: rs727502823
NCBI 1000 Genomes Browser:
rs727502823
Molecular consequence:
  • NM_006796.3:c.1875G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spinocerebellar ataxia type 28 (SCA28)
Identifiers:
MONDO: MONDO:0012450; MedGen: C1853249; Orphanet: 101109; OMIM: 610246

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002548426Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(May 3, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.

Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, Joensuu T, Canafoglia L, Franceschetti S, Michelucci R, Markkinen S, Heron SE, Hildebrand MS, Andermann E, Andermann F, Gambardella A, Tinuper P, Licchetta L, Scheffer IE, Criscuolo C, Filla A, Ferlazzo E, et al.

Nat Genet. 2015 Jan;47(1):39-46. doi: 10.1038/ng.3144. Epub 2014 Nov 17.

PubMed [citation]
PMID:
25401298
PMCID:
PMC4281260

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548426.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: AFG3L2 c.1875G>A (p.Met625Ile) results in a conservative amino acid change located in the Peptidase M41 domain (IPR000642) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251482 control chromosomes (gnomAD). c.1875G>A has been reported in the literature in two unrelated homozygous individuals affected with Progressive Myoclonus Epilepsy (Muona_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed this variant since 2014: the variant was classified as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 23, 2024