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NM_152564.5(VPS13B):c.8756A>G (p.Gln2919Arg) AND Cohen syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 11, 2022
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:
RCV001364534.3

Allele description [Variation Report for NM_152564.5(VPS13B):c.8756A>G (p.Gln2919Arg)]

NM_152564.5(VPS13B):c.8756A>G (p.Gln2919Arg)

Gene:
VPS13B:vacuolar protein sorting 13 homolog B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q22.2
Genomic location:
Preferred name:
NM_152564.5(VPS13B):c.8756A>G (p.Gln2919Arg)
HGVS:
  • NC_000008.11:g.99819546A>G
  • NG_007098.2:g.811281A>G
  • NM_017890.5:c.8831A>G
  • NM_152564.5:c.8756A>GMANE SELECT
  • NP_060360.3:p.Gln2944Arg
  • NP_689777.3:p.Gln2919Arg
  • LRG_351:g.811281A>G
  • NC_000008.10:g.100831774A>G
Protein change:
Q2919R
Links:
dbSNP: rs987741026
NCBI 1000 Genomes Browser:
rs987741026
Molecular consequence:
  • NM_017890.5:c.8831A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152564.5:c.8756A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cohen syndrome (COH1)
Synonyms:
Pepper syndrome; Cutis verticis gyrata, retinitis pigmentosa, and sensorineural deafness
Identifiers:
MONDO: MONDO:0008999; MedGen: C0265223; Orphanet: 193; OMIM: 216550

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001560687Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 11, 2022) 		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, SCV001560687.2

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

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 2944 of the VPS13B protein (p.Gln2944Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1055803). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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