NM_002693.2(POLG):c.1229_1231delAGC (p.Gln410del) AND Progressive sclerosing poliodystrophy

Clinical significance:Uncertain significance (Last evaluated: Oct 1, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000704825.1

Allele description [Variation Report for NM_002693.2(POLG):c.1229_1231delAGC (p.Gln410del)]

NM_002693.2(POLG):c.1229_1231delAGC (p.Gln410del)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.2(POLG):c.1229_1231delAGC (p.Gln410del)
HGVS:
  • NC_000015.10:g.89328475_89328477delGCT
  • NM_002693.2:c.1229_1231delAGC
  • NP_002684.1:p.Gln410del
  • LRG_765t1:c.1229_1231del
  • LRG_765:g.11319_11321del
  • LRG_765p1:p.Gln410del
  • NC_000015.9:g.89871706_89871708delGCT
  • NM_002693.2:c.1229_1231del
Protein change:
Q410del
Links:
dbSNP: rs765446994
NCBI 1000 Genomes Browser:
rs765446994

Condition(s)

Name:
Progressive sclerosing poliodystrophy (MTDPS4A)
Synonyms:
Alpers Syndrome; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers-Huttenlocher Syndrome
Identifiers:
MedGen: C0205710; Orphanet: 726; OMIM: 203700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000833794Invitaecriteria provided, single submitter
Uncertain significance
(Jun 8, 2018)
germlineclinical testing

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

SCV000887140Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicinecriteria provided, single submitter
Uncertain significance
(Oct 1, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV000833794.1

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

Description

This variant, c.1229_1231delAGC, results in the deletion of 1 amino acid of the POLG protein (p.Gln410del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs765446994, ExAC 0.009%). This variant has not been reported in the literature in individuals with POLG-related disease. ClinVar contains an entry for this variant (Variation ID: 449625). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Wong Mito Lab, Molecular and Human Genetics,Baylor College of Medicine, SCV000887140.1

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

Description

The NM_002693.2:c.1229_1231del (NP_002684.1:p.Gln410del) [GRCH38: NC_000015.10:g.89328482_89328484del] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. BP3:This variant results in inframe indel in repeats without known function. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance.

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

Last Updated: Apr 17, 2019

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