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NM_020158.4(EXOSC5):c.617T>A (p.Leu206His) AND Cerebellar ataxia, brain abnormalities, and cardiac conduction defects

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 21, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001731249.1

Allele description [Variation Report for NM_020158.4(EXOSC5):c.617T>A (p.Leu206His)]

NM_020158.4(EXOSC5):c.617T>A (p.Leu206His)

Gene:
EXOSC5:exosome component 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_020158.4(EXOSC5):c.617T>A (p.Leu206His)
Other names:
L206H
HGVS:
  • NC_000019.10:g.41386724A>T
  • NM_020158.4:c.617T>AMANE SELECT
  • NP_064543.3:p.Leu206His
  • NC_000019.9:g.41892629A>T
  • NM_020158.3:c.617T>A
Protein change:
LEU206HIS
Links:
OMIM: 606492.0003; dbSNP: rs2123217925
NCBI 1000 Genomes Browser:
rs2123217925
Molecular consequence:
  • NM_020158.4:c.617T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cerebellar ataxia, brain abnormalities, and cardiac conduction defects
Identifiers:
MONDO: MONDO:0859200; MedGen: C5562005; OMIM: 619576

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001981693OMIM
no assertion criteria provided
Pathogenic
(Oct 21, 2021) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Biallelic variants in the RNA exosome gene EXOSC5 are associated with developmental delays, short stature, cerebellar hypoplasia and motor weakness.

Slavotinek A, Misceo D, Htun S, Mathisen L, Frengen E, Foreman M, Hurtig JE, Enyenihi L, Sterrett MC, Leung SW, Schneidman-Duhovny D, Estrada-Veras J, Duncan JL, Haaxma CA, Kamsteeg EJ, Xia V, Beleford D, Si Y, Douglas G, Treidene HE, van Hoof A, Fasken MB, et al.

Hum Mol Genet. 2020 Aug 3;29(13):2218-2239. doi: 10.1093/hmg/ddaa108.

PubMed [citation]
PMID:
32504085
PMCID:
PMC7399534

Details of each submission

From OMIM, SCV001981693.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an 11-month-old boy (patient 2), born of consanguineous Iraqi parents, with cerebellar ataxia, brain abnormalities, and cardiac conduction defects (CABAC; 619576), Slavotinek et al. (2020) identified a homozygous c.617T-A transversion (c.617T-A, NM_020158.3) in the EXOSC5 gene, resulting in a leu206-to-his (L206H) substitution at a conserved residue. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database. In vitro immunoprecipitation studies showed that the mutation caused altered interactions with other RNA exosome subunits, and functional expression studies showed that the mutation caused growth defects in yeast.

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

Last Updated: Jul 15, 2024