NM_000310.4(PPT1):c.628-2A>G AND Neuronal ceroid lipofuscinosis 1

Clinical significance:Likely pathogenic (Last evaluated: Aug 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001378615.1

Allele description [Variation Report for NM_000310.4(PPT1):c.628-2A>G]

NM_000310.4(PPT1):c.628-2A>G

Gene:
PPT1:palmitoyl-protein thioesterase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.2
Genomic location:
Preferred name:
NM_000310.4(PPT1):c.628-2A>G
HGVS:
  • NC_000001.11:g.40078660T>C
  • NG_009192.1:g.23811A>G
  • NM_000310.4:c.628-2A>GMANE SELECT
  • NM_001142604.2:c.319-2A>G
  • NM_001363695.2:c.628-2A>G
  • LRG_690:g.23811A>G
  • NC_000001.10:g.40544332T>C
Molecular consequence:
  • NM_000310.4:c.628-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001142604.2:c.319-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363695.2:c.628-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis 1 (CLN1)
Synonyms:
CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET; CLN1 variable age at onset; Infantile CLN (type of CLN1); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009744; MedGen: C1850451; OMIM: 256730

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001576219Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 27, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1).

Salonen T, Järvelä I, Peltonen L, Jalanko A.

Hum Mutat. 2000;15(3):273-9.

PubMed [citation]
PMID:
10679943
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001576219.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 6 of the PPT1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PPT1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943, 21990111). 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.

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

Last Updated: Oct 7, 2021

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