NM_152564.5(VPS13B):c.10001_10002del (p.Thr3334fs) AND Cohen syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 22, 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:: RCV000050041.9

Allele description [Variation Report for NM_152564.5(VPS13B):c.10001_10002del (p.Thr3334fs)]

NM_152564.5(VPS13B):c.10001_10002del (p.Thr3334fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

8q22.2

Genomic location:

Preferred name:

NM_152564.5(VPS13B):c.10001_10002del (p.Thr3334fs)

HGVS:

NC_000008.11:g.99848832CA[1]
NG_007098.2:g.840567CA[1]
NM_017890.5:c.10076_10077del
NM_152564.5:c.10001_10002delMANE SELECT
NP_060360.3:p.Thr3359fs
NP_689777.3:p.Thr3334fs
LRG_351:g.840567CA[1]
NC_000008.10:g.100861060CA[1]
NC_000008.10:g.100861060_100861061del
NM_017890.4:c.10076_10077delCA

Protein change:

T3334fs

Links:

dbSNP: rs386834054

NCBI 1000 Genomes Browser:

rs386834054

Molecular consequence:

NM_017890.5:c.10076_10077del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152564.5:c.10001_10002del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV000082450	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	Likely pathogenic	unknown	not provided
SCV001432377	Service de Génétique Moléculaire, Hôpital Robert Debré	no assertion criteria provided	Likely pathogenic	unknown	clinical testing
SCV002243712	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 22, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15141358, 16648375, 20461111, 17990063, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000082450

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

no assertion criteria provided

Likely pathogenic

unknown

not provided

SCV001432377

Service de Génétique Moléculaire, Hôpital Robert Debré

no assertion criteria provided

Likely pathogenic

unknown

clinical testing

SCV002243712

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 22, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	yes	not provided	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.

Kolehmainen J, Wilkinson R, Lehesjoki AE, Chandler K, Kivitie-Kallio S, Clayton-Smith J, Träskelin AL, Waris L, Saarinen A, Khan J, Gross-Tsur V, Traboulsi EI, Warburg M, Fryns JP, Norio R, Black GC, Manson FD.

Am J Hum Genet. 2004 Jul;75(1):122-7. Epub 2004 May 12.

PubMed [citation]

PMID:: 15141358
PMCID:: PMC1181995

Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome.

Seifert W, Holder-Espinasse M, Spranger S, Hoeltzenbein M, Rossier E, Dollfus H, Lacombe D, Verloes A, Chrzanowska KH, Maegawa GH, Chitayat D, Kotzot D, Huhle D, Meinecke P, Albrecht B, Mathijssen I, Leheup B, Raile K, Hennies HC, Horn D.

J Med Genet. 2006 May;43(5):e22.

PubMed [citation]

PMID:: 16648375
PMCID:: PMC2564527

See all PubMed Citations (5)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082450.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

Description

Converted during submission from probable-pathogenic to Likely pathogenic.

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

From Service de Génétique Moléculaire, Hôpital Robert Debré, SCV001432377.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002243712.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Thr3359Serfs*29) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Cohen syndrome (PMID: 17990063). This variant is also known as c.10074_ 10075delCA (p.G3358fs29). ClinVar contains an entry for this variant (Variation ID: 56628). For these reasons, this variant has been classified as Pathogenic.

#	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 8, 2025

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