NM_014780.5(CUL7):c.2130_2131delinsTGCCTG (p.Cys711fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 3, 2021
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:: RCV000519666.3

Allele description [Variation Report for NM_014780.5(CUL7):c.2130_2131delinsTGCCTG (p.Cys711fs)]

NM_014780.5(CUL7):c.2130_2131delinsTGCCTG (p.Cys711fs)

Gene:

CUL7:cullin 7 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_014780.5(CUL7):c.2130_2131delinsTGCCTG (p.Cys711fs)

HGVS:

NC_000006.12:g.43048186_43048187delinsCAGGCA
NG_016205.1:g.10759_10760delinsTGCCTG
NM_001168370.2:c.2226_2227delinsTGCCTG
NM_001374872.1:c.2226_2227delinsTGCCTG
NM_001374873.1:c.2130_2131delinsTGCCTG
NM_001374874.1:c.2130_2131delinsTGCCTG
NM_014780.5:c.2130_2131delinsTGCCTGMANE SELECT
NP_001161842.2:p.Cys743fs
NP_001361801.1:p.Cys743fs
NP_001361802.1:p.Cys711fs
NP_001361803.1:p.Cys711fs
NP_055595.2:p.Cys711fs
NC_000006.11:g.43015924_43015925delinsCAGGCA
NM_014780.4:c.2130_2131delCTinsTGCCTG

Protein change:

C711fs

Links:

dbSNP: rs1554138553

NCBI 1000 Genomes Browser:

rs1554138553

Molecular consequence:

NM_001168370.2:c.2226_2227delinsTGCCTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374872.1:c.2226_2227delinsTGCCTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374873.1:c.2130_2131delinsTGCCTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374874.1:c.2130_2131delinsTGCCTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014780.5:c.2130_2131delinsTGCCTG - 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
SCV000619259	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 19, 2017)	germline	clinical testing	Citation Link,
SCV004673044	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 3, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16142236, 17675530, 19225462, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000619259

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 19, 2017)

germline

clinical testing

Citation Link,

SCV004673044

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 3, 2021)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of mutations in CUL7 in 3-M syndrome.

Huber C, Dias-Santagata D, Glaser A, O'Sullivan J, Brauner R, Wu K, Xu X, Pearce K, Wang R, Uzielli ML, Dagoneau N, Chemaitilly W, Superti-Furga A, Dos Santos H, Mégarbané A, Morin G, Gillessen-Kaesbach G, Hennekam R, Van der Burgt I, Black GC, Clayton PE, Read A, et al.

Nat Genet. 2005 Oct;37(10):1119-24. Epub 2005 Sep 4.

PubMed [citation]

PMID:: 16142236

Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia.

Maksimova N, Hara K, Miyashia A, Nikolaeva I, Shiga A, Nogovicina A, Sukhomyasova A, Argunov V, Shvedova A, Ikeuchi T, Nishizawa M, Kuwano R, Onodera O.

J Med Genet. 2007 Dec;44(12):772-8. Epub 2007 Aug 3.

PubMed [citation]

PMID:: 17675530
PMCID:: PMC2652813

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000619259.1

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

Description

The c.2130_2131delCTinsTGCCTG variant in the CUL7 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Cysteine 711, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Cys711AlafsX12. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2130_2131delCTinsTGCCTG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.2130_2131delCTinsTGCCTG as a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004673044.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CUL7-related conditions. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change creates a premature translational stop signal (p.Cys711Alafs*12) in the CUL7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CUL7 are known to be pathogenic (PMID: 16142236, 17675530, 19225462).

#	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: Oct 26, 2024

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