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NM_001128159.3(VPS53):c.1312_1313+2del AND Pontoneocerebellar hypoplasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 17, 2021
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:
RCV001731871.1

Allele description [Variation Report for NM_001128159.3(VPS53):c.1312_1313+2del]

NM_001128159.3(VPS53):c.1312_1313+2del

Gene:
VPS53:VPS53 subunit of GARP complex [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17p13.3
Genomic location:
Preferred name:
NM_001128159.3(VPS53):c.1312_1313+2del
HGVS:
  • NC_000017.11:g.586268_586271del
  • NG_034190.1:g.133586_133589del
  • NM_001128159.3:c.1312_1313+2delMANE SELECT
  • NM_001366253.2:c.1312_1313+2del
  • NM_001366254.2:c.718_719+2del
  • NM_018289.4:c.1225_1226+2del
  • NC_000017.10:g.489508_489511del
  • NM_001128159.2:c.1312_1313+2delAAGT
Links:
dbSNP: rs768997239
NCBI 1000 Genomes Browser:
rs768997239
Molecular consequence:
  • NM_001128159.3:c.1312_1313+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001366253.2:c.1312_1313+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001366254.2:c.718_719+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_018289.4:c.1225_1226+2del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Pontoneocerebellar hypoplasia
Synonyms:
Pontocerebellar hypoplasia; Non-syndromic pontocerebellar hypoplasia
Identifiers:
MONDO: MONDO:0020135; MedGen: C1261175; Orphanet: 98523; OMIM: PS607596

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001983532Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Sep 17, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983532.1

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

Description

Variant summary: VPS53 c.1312_1313+2delAAGT is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5` splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.8e-05 in 251362 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1312_1313+2delAAGT in individuals affected with Pontocerebellar Hypoplasia, Type 2E and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Mar 4, 2023