NM_152564.5(VPS13B):c.11839_11842dup (p.Ser3948fs) AND Cohen syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 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:: RCV001067905.8

Allele description [Variation Report for NM_152564.5(VPS13B):c.11839_11842dup (p.Ser3948fs)]

NM_152564.5(VPS13B):c.11839_11842dup (p.Ser3948fs)

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.11839_11842dup (p.Ser3948fs)

HGVS:

NC_000008.11:g.99875511_99875514dup
NG_007098.2:g.867246_867249dup
NM_017890.5:c.11914_11917dup
NM_152564.5:c.11839_11842dupMANE SELECT
NP_060360.3:p.Ser3973fs
NP_060360.3:p.Ser3973fs
NP_689777.3:p.Ser3948fs
LRG_351t1:c.11914_11917dup
LRG_351:g.867246_867249dup
LRG_351p1:p.Ser3973fs
NC_000008.10:g.100887737_100887738insTTCT
NC_000008.10:g.100887739_100887742dup
NM_017890.4:c.11914_11917dup

Protein change:

S3948fs

Links:

dbSNP: rs1817657601

NCBI 1000 Genomes Browser:

rs1817657601

Molecular consequence:

NM_017890.5:c.11914_11917dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152564.5:c.11839_11842dup - 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

Recent activity

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Mus musculus transmembrane protein 19 (Tmem19), transcript variant 8, mRNA
Mus musculus transmembrane protein 19 (Tmem19), transcript variant 8, mRNA
gi|2719984454|ref|NM_001429446.1|

Nucleotide
Homologene neighbors for GEO Profiles (Select 78983268) (0)
GEO Profiles
Homologene neighbors for GEO Profiles (Select 78947029) (0)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 78978865) (20)
GEO Profiles
TTBK2 tau tubulin kinase 2 [Homo sapiens]
TTBK2 tau tubulin kinase 2 [Homo sapiens]
Gene ID:146057

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001232989	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 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

SCV001232989

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 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, SCV001232989.5

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

Description

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. ClinVar contains an entry for this variant (Variation ID: 861389). 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.Ser3973Phefs*20) in the VPS13B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 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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