NM_014363.6(SACS):c.8793del (p.Lys2931fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 9, 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:
RCV000519077.3

Allele description [Variation Report for NM_014363.6(SACS):c.8793del (p.Lys2931fs)]

NM_014363.6(SACS):c.8793del (p.Lys2931fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.8793del (p.Lys2931fs)
HGVS:
  • NC_000013.11:g.23335089del
  • NG_012342.1:g.103620del
  • NM_001278055.2:c.8352del
  • NM_014363.6:c.8793delMANE SELECT
  • NP_001264984.1:p.Lys2784fs
  • NP_055178.3:p.Lys2931fs
  • NC_000013.10:g.23909222del
  • NC_000013.10:g.23909228del
  • NM_014363.4:c.8793del
  • NM_014363.4:c.8793delA
  • NM_014363.5:c.8793del
  • NM_014363.5:c.8793delA
Protein change:
K2784fs
Links:
dbSNP: rs767871841
NCBI 1000 Genomes Browser:
rs767871841
Molecular consequence:
  • NM_001278055.2:c.8352del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.8793del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000617740GeneDxcriteria provided, single submitter
Likely pathogenic
(Nov 9, 2018)
germlineclinical testing

Citation Link,

SCV001145350Athena Diagnostics Inccriteria provided, single submitter
Pathogenic
(Sep 18, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Sacsin-related autosomal recessive ataxia without prominent retinal myelinated fibers in Japan.

Hara K, Onodera O, Endo M, Kondo H, Shiota H, Miki K, Tanimoto N, Kimura T, Nishizawa M.

Mov Disord. 2005 Mar;20(3):380-2.

PubMed [citation]
PMID:
15486997

Sacsin-related ataxia caused by the novel nonsense mutation Arg4325X.

Yamamoto Y, Nakamori M, Konaka K, Nagano S, Shimazaki H, Takiyama Y, Sakoda S.

J Neurol. 2006 Oct;253(10):1372-3. Epub 2006 Aug 29. No abstract available.

PubMed [citation]
PMID:
16944349
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000617740.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.8793delA variant in the SACS gene has been reported previously in two siblings with spastic ataxia who were homozygous for the c.8793delA variant (Hara et al., 2005). The c.8793delA variant causes a frameshift starting with codon Lysine 2931, changes this amino acid to a Asparagine residue, and creates a premature Stop codon at position 22 of the new reading frame, denoted p.Lys2931AsnfsX22. This variant is predicted to cause loss of normal protein function through protein truncation. The c.8793delA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.8793delA as a likely pathogenic variant.

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

From Athena Diagnostics Inc, SCV001145350.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The variant results in a shift of the reading frame, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.

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

Last Updated: Oct 16, 2021

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