NM_003384.3(VRK1):c.586G>C (p.Val196Leu) AND Pontocerebellar hypoplasia type 1A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV002563024.8

Allele description [Variation Report for NM_003384.3(VRK1):c.586G>C (p.Val196Leu)]

NM_003384.3(VRK1):c.586G>C (p.Val196Leu)

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.586G>C (p.Val196Leu)

HGVS:

NC_000014.9:g.96855233G>C
NG_016293.1:g.62887G>C
NM_003384.3:c.586G>CMANE SELECT
NP_003375.1:p.Val196Leu
NC_000014.8:g.97321570G>C
NM_003384.2:c.586G>C

Protein change:

V196L

Links:

dbSNP: rs372089106

NCBI 1000 Genomes Browser:

rs372089106

Molecular consequence:

NM_003384.3:c.586G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pontocerebellar hypoplasia type 1A (PCH1A)
Synonyms:: Pontocerebellar hypoplasia with infantile spinal muscular atrophy; Pontocerebellar hypoplasia with anterior horn cell disease
Identifiers:: Gene: 100852400; MONDO: MONDO:0011866; MedGen: C1843504; Orphanet: 2254; Orphanet: 88616; OMIM: 607596

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001394021	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001394021

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001394021.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces valine with leucine at codon 196 of the VRK1 protein (p.Val196Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs372089106, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. 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: "Benign"; Align-GVGD: "Class C25"). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 2, 2024

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