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NM_001378743.1(CYLD):c.1112C>A (p.Ser371Ter) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 13, 2024
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:
RCV000760471.2

Allele description

NM_001378743.1(CYLD):c.1112C>A (p.Ser371Ter)

Gene:
CYLD:CYLD lysine 63 deubiquitinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q12.1
Genomic location:
Preferred name:
NM_001378743.1(CYLD):c.1112C>A (p.Ser371Ter)
HGVS:
  • NC_000016.10:g.50777915C>A
  • NG_012061.1:g.40866C>A
  • NM_001042355.2:c.1103C>A
  • NM_001042412.3:c.1103C>A
  • NM_001378743.1:c.1112C>AMANE SELECT
  • NM_001378744.1:c.1103C>A
  • NM_001378745.1:c.1103C>A
  • NM_001378746.1:c.1103C>A
  • NM_001378747.1:c.1103C>A
  • NM_001378748.1:c.1103C>A
  • NM_001378749.1:c.1103C>A
  • NM_001378750.1:c.1103C>A
  • NM_001378751.1:c.1103C>A
  • NM_001378752.1:c.1103C>A
  • NM_001378753.1:c.1103C>A
  • NM_001378754.1:c.437C>A
  • NM_001378755.1:c.437C>A
  • NM_015247.3:c.1112C>A
  • NP_001035814.1:p.Ser368Ter
  • NP_001035877.1:p.Ser368Ter
  • NP_001365672.1:p.Ser371Ter
  • NP_001365673.1:p.Ser368Ter
  • NP_001365674.1:p.Ser368Ter
  • NP_001365675.1:p.Ser368Ter
  • NP_001365676.1:p.Ser368Ter
  • NP_001365677.1:p.Ser368Ter
  • NP_001365678.1:p.Ser368Ter
  • NP_001365679.1:p.Ser368Ter
  • NP_001365680.1:p.Ser368Ter
  • NP_001365681.1:p.Ser368Ter
  • NP_001365682.1:p.Ser368Ter
  • NP_001365683.1:p.Ser146Ter
  • NP_001365684.1:p.Ser146Ter
  • NP_056062.1:p.Ser371Ter
  • NP_056062.1:p.Ser371Ter
  • LRG_491t1:c.1112C>A
  • LRG_491:g.40866C>A
  • LRG_491p1:p.Ser371Ter
  • NC_000016.9:g.50811826C>A
  • NM_015247.2:c.1112C>A
  • NR_166071.1:n.1367C>A
  • p.[Ser371*]
Protein change:
S146*
Links:
dbSNP: rs886040872
NCBI 1000 Genomes Browser:
rs886040872
Molecular consequence:
  • NR_166071.1:n.1367C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001042355.2:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001042412.3:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378743.1:c.1112C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378744.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378745.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378746.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378747.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378748.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378749.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378750.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378751.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378752.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378753.1:c.1103C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378754.1:c.437C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001378755.1:c.437C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_015247.3:c.1112C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000890360GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Pathogenic
(Dec 18, 2018)
germlineclinical testing

Citation Link,

SCV004297725Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 13, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling.

Blake PW, Toro JR.

Hum Mutat. 2009 Jul;30(7):1025-36. doi: 10.1002/humu.21024. Review.

PubMed [citation]
PMID:
19462465
PMCID:
PMC3243308

Identification of the familial cylindromatosis tumour-suppressor gene.

Bignell GR, Warren W, Seal S, Takahashi M, Rapley E, Barfoot R, Green H, Brown C, Biggs PJ, Lakhani SR, Jones C, Hansen J, Blair E, Hofmann B, Siebert R, Turner G, Evans DG, Schrander-Stumpel C, Beemer FA, van Den Ouweland A, Halley D, Delpech B, et al.

Nat Genet. 2000 Jun;25(2):160-5.

PubMed [citation]
PMID:
10835629
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000890360.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The S371X variant in the CYLD gene has been reported previously in multiple unrelated individuals with either Brooke-Spiegler syndrome, familial cylindromatosis, or multiple familial trichoepitheliomas (Bignell et al., 2000; Bowen et al., 2005; Kazakov et al., 2011; Linos et al., 2011; Grossman et al., 2013; Lv et al., 2014; Dubois et al., 2017; Monteiro et al., 2018a; Monteiro et al., 2018b). The S371X is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The S371X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret S371X as a pathogenic variant.

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

From Invitae, SCV004297725.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Ser371*) in the CYLD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYLD are known to be pathogenic (PMID: 19462465). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with familial cylindromatosis (PMID: 10835629). ClinVar contains an entry for this variant (Variation ID: 267232). 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 16, 2024