NM_152564.5(VPS13B):c.11886dup (p.Ser3963fs) AND Cohen syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 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:: RCV003068500.3

Allele description [Variation Report for NM_152564.5(VPS13B):c.11886dup (p.Ser3963fs)]

NM_152564.5(VPS13B):c.11886dup (p.Ser3963fs)

Gene:

VPS13B:vacuolar protein sorting 13 homolog B [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

8q22.2

Genomic location:

Preferred name:

NM_152564.5(VPS13B):c.11886dup (p.Ser3963fs)

HGVS:

NC_000008.11:g.99875558dup
NG_007098.2:g.867293dup
NM_017890.5:c.11961dup
NM_152564.5:c.11886dupMANE SELECT
NP_060360.3:p.Ser3988Leufs
NP_060360.3:p.Ser3988fs
NP_689777.3:p.Ser3963Leufs
NP_689777.3:p.Ser3963fs
LRG_351t1:c.11961dup
LRG_351t2:c.11886dup
LRG_351:g.867293dup
LRG_351p1:p.Ser3988Leufs
LRG_351p2:p.Ser3963Leufs
NC_000008.10:g.100887780_100887781insC
NC_000008.10:g.100887786dup
NM_017890.4:c.11961dup
NM_152564.4:c.11886dup

Protein change:

S3963fs

Molecular consequence:

NM_017890.5:c.11961dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152564.5:c.11886dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003456794	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	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

SCV003456794

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003456794.2

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

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the VPS13B protein in which other variant(s) (p.Lys3991Leufs*23) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This sequence change creates a premature translational stop signal (p.Ser3988Leufs*4) in the VPS13B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the VPS13B protein.

#	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: Sep 29, 2024

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