NM_005869.4(CWC27):c.1002dup (p.Val335fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 8, 2024
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:: RCV001230037.7

Allele description [Variation Report for NM_005869.4(CWC27):c.1002dup (p.Val335fs)]

NM_005869.4(CWC27):c.1002dup (p.Val335fs)

Gene:

CWC27:CWC27 spliceosome associated cyclophilin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

5q12.3

Genomic location:

Preferred name:

NM_005869.4(CWC27):c.1002dup (p.Val335fs)

HGVS:

NC_000005.10:g.64885506dup
NM_001297644.1:c.1002dup
NM_001364478.1:c.1002dup
NM_005869.4:c.1002dupMANE SELECT
NP_001284573.1:p.Val335fs
NP_001351407.1:p.Val335fs
NP_005860.2:p.Val335fs
NC_000005.9:g.64181325_64181326insA
NC_000005.9:g.64181333dup
NM_005869.3:c.1002dup
NM_005869.3:c.1002dupA

Protein change:

V335fs

Links:

OMIM: 617170.0003; dbSNP: rs752159903

NCBI 1000 Genomes Browser:

rs752159903

Molecular consequence:

NM_001297644.1:c.1002dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364478.1:c.1002dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005869.4:c.1002dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001402504	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28285769, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402504

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2024)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.

Xu M, Xie YA, Abouzeid H, Gordon CT, Fiorentino A, Sun Z, Lehman A, Osman IS, Dharmat R, Riveiro-Alvarez R, Bapst-Wicht L, Babino D, Arno G, Busetto V, Zhao L, Li H, Lopez-Martinez MA, Azevedo LF, Hubert L, Pontikos N, Eblimit A, Lorda-Sanchez I, et al.

Am J Hum Genet. 2017 Apr 6;100(4):592-604. doi: 10.1016/j.ajhg.2017.02.008. Epub 2017 Mar 9.

PubMed [citation]

PMID:: 28285769
PMCID:: PMC5384039

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, SCV001402504.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Val335Serfs*13) in the CWC27 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CWC27 are known to be pathogenic (PMID: 28285769). 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 retinal degeneration (PMID: 28285769). ClinVar contains an entry for this variant (Variation ID: 426073). 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: Nov 10, 2024

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