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NM_152564.5(VPS13B):c.9940_9941insTTT (p.Gln3314delinsLeuTer) AND Cohen syndrome

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Dec 9, 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:
RCV000668681.3

Allele description [Variation Report for NM_152564.5(VPS13B):c.9940_9941insTTT (p.Gln3314delinsLeuTer)]

NM_152564.5(VPS13B):c.9940_9941insTTT (p.Gln3314delinsLeuTer)

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.9940_9941insTTT (p.Gln3314delinsLeuTer)
HGVS:
  • NC_000008.11:g.99835736_99835737insTTT
  • NG_007098.2:g.827471_827472insTTT
  • NM_017890.5:c.10015_10016insTTT
  • NM_152564.5:c.9940_9941insTTTMANE SELECT
  • NP_060360.3:p.Gln3339delinsLeuTer
  • NP_060360.3:p.Gln3339delinsLeuTer
  • NP_689777.3:p.Gln3314delinsLeuTer
  • LRG_351t1:c.10015_10016insTTT
  • LRG_351:g.827471_827472insTTT
  • LRG_351p1:p.Gln3339delinsLeuTer
  • NC_000008.10:g.100847964_100847965insTTT
  • NM_017890.4:c.10015_10016insTTT
Links:
dbSNP: rs1301330402
NCBI 1000 Genomes Browser:
rs1301330402
Molecular consequence:
  • NM_017890.5:c.10015_10016insTTT - nonsense - [Sequence Ontology: SO:0001587]
  • NM_152564.5:c.9940_9941insTTT - nonsense - [Sequence Ontology: SO:0001587]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000793322Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))		Likely pathogenic
(Aug 10, 2017) 		unknownclinical testing

Citation Link,

SCV004679084Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 9, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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, SCV000793322.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004679084.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Gln3339delinsLeu*) 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 present in population databases (no rsID available, gnomAD 0.0009%). 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: 553273). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024