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NM_002693.3(POLG):c.1942_1943delinsAG (p.Pro648Ser) AND Progressive sclerosing poliodystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 2, 2023
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:
RCV003626237.2

Allele description [Variation Report for NM_002693.3(POLG):c.1942_1943delinsAG (p.Pro648Ser)]

NM_002693.3(POLG):c.1942_1943delinsAG (p.Pro648Ser)

Gene:
POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_002693.3(POLG):c.1942_1943delinsAG (p.Pro648Ser)
HGVS:
  • NC_000015.10:g.89325456_89325457delinsCT
  • NG_008218.2:g.14339_14340delinsAG
  • NM_001126131.2:c.1942_1943delinsAG
  • NM_002693.3:c.1942_1943delinsAGMANE SELECT
  • NP_001119603.1:p.Pro648Ser
  • NP_002684.1:p.Pro648Ser
  • NP_002684.1:p.Pro648Ser
  • LRG_765t1:c.1942_1943delCCinsAG
  • LRG_765:g.14339_14340delinsAG
  • LRG_765p1:p.Pro648Ser
  • NC_000015.9:g.89868687_89868688delinsCT
  • NM_002693.2:c.1942_1943delCCinsAG
Protein change:
P648S
Molecular consequence:
  • NM_001126131.2:c.1942_1943delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002693.3:c.1942_1943delinsAG - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Progressive sclerosing poliodystrophy (MTDPS4A)
Synonyms:
Alpers disease; Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis; Alpers progressive infantile poliodystrophy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008758; MedGen: C0205710; Orphanet: 726; OMIM: 203700

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004463537Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(May 2, 2023) 		germlineclinical testing

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

Help

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. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004463537.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. A different variant (c.1942C>T) giving rise to the same protein effect has been determined to be pathogenic (Invitae). This suggests that this variant is also likely to be causative of disease. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 648 of the POLG protein (p.Pro648Ser).

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

Last Updated: Sep 29, 2024