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NM_003384.3(VRK1):c.1070A>T (p.Lys357Met) AND Congenital pontocerebellar hypoplasia type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 5, 2018
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:
RCV000801726.3

Allele description [Variation Report for NM_003384.3(VRK1):c.1070A>T (p.Lys357Met)]

NM_003384.3(VRK1):c.1070A>T (p.Lys357Met)

Gene:
VRK1:VRK serine/threonine kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.2
Genomic location:
Preferred name:
NM_003384.3(VRK1):c.1070A>T (p.Lys357Met)
HGVS:
  • NC_000014.9:g.96876031A>T
  • NG_016293.1:g.83685A>T
  • NM_003384.3:c.1070A>TMANE SELECT
  • NP_003375.1:p.Lys357Met
  • NC_000014.8:g.97342368A>T
  • NM_003384.2:c.1070A>T
Protein change:
K357M
Links:
dbSNP: rs1595691552
NCBI 1000 Genomes Browser:
rs1595691552
Molecular consequence:
  • NM_003384.3:c.1070A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital pontocerebellar hypoplasia type 1
Synonyms:
Pontocerebellar hypoplasia type 1
Identifiers:
MONDO: MONDO:0016396; MedGen: C5442006; Orphanet: 2254

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000941518Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 5, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000941518.1

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

Description

This sequence change replaces lysine with methionine at codon 357 of the VRK1 protein (p.Lys357Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VRK1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024