NM_152564.5(VPS13B):c.7311_7312insAGGCA (p.Ala2438fs) AND Cohen syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000672503.6

Allele description [Variation Report for NM_152564.5(VPS13B):c.7311_7312insAGGCA (p.Ala2438fs)]

NM_152564.5(VPS13B):c.7311_7312insAGGCA (p.Ala2438fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

8q22.2

Genomic location:

Preferred name:

NM_152564.5(VPS13B):c.7311_7312insAGGCA (p.Ala2438fs)

HGVS:

NC_000008.11:g.99776838_99776839insAGGCA
NG_007098.2:g.768573_768574insAGGCA
NM_017890.5:c.7386_7387insAGGCA
NM_152564.5:c.7311_7312insAGGCAMANE SELECT
NP_060360.3:p.Ala2463fs
NP_689777.3:p.Ala2438fs
LRG_351:g.768573_768574insAGGCA
NC_000008.10:g.100789066_100789067insAGGCA
NM_017890.4:c.7386_7387ins5

Protein change:

A2438fs

Links:

dbSNP: rs1554952465

NCBI 1000 Genomes Browser:

rs1554952465

Molecular consequence:

NM_017890.5:c.7386_7387insAGGCA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152564.5:c.7311_7312insAGGCA - 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
SCV000797612	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Feb 1, 2018)	unknown	clinical testing	Citation Link,
SCV002165567	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15141358, 16648375, 20461111, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000797612

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Feb 1, 2018)

unknown

clinical testing

Citation Link,

SCV002165567

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 27, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	unknown	not provided	not provided	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 (4)

Details of each submission

From Counsyl, SCV000797612.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002165567.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

ClinVar contains an entry for this variant (Variation ID: 556489). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala2463Argfs*39) 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).

#	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: Apr 7, 2025

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