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NM_001128159.3(VPS53):c.1704+1G>A AND Pontoneocerebellar hypoplasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 24, 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:
RCV003155873.1

Allele description [Variation Report for NM_001128159.3(VPS53):c.1704+1G>A]

NM_001128159.3(VPS53):c.1704+1G>A

Genes:
LOC126862456:CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:463241-464440 [Gene]
VPS53:VPS53 subunit of GARP complex [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.3
Genomic location:
Preferred name:
NM_001128159.3(VPS53):c.1704+1G>A
HGVS:
  • NC_000017.11:g.560425C>T
  • NG_034190.1:g.159432G>A
  • NG_086954.1:g.525C>T
  • NM_001128159.3:c.1704+1G>AMANE SELECT
  • NM_001366253.2:c.1704+1G>A
  • NM_001366254.2:c.1110+1G>A
  • NM_018289.4:c.1617+1G>A
  • NC_000017.10:g.463665C>T
  • NM_001128159.2:c.1704+1G>A
Molecular consequence:
  • NM_001128159.3:c.1704+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001366253.2:c.1704+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001366254.2:c.1110+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_018289.4:c.1617+1G>A - 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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003845164Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Feb 24, 2023) 		germlineclinical testing

Citation Link

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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, SCV003845164.1

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

Description

Variant summary: VPS53 c.1704+1G>A 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 was absent in 248988 control chromosomes. To our knowledge, no occurrence of c.1704+1G>A in individuals affected with Pontocerebellar Hypoplasia, Type 2E and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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: Jun 10, 2023