NM_007194.4(CHEK2):c.1011C>A (p.Tyr337Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 24, 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:: RCV000424411.5

Allele description [Variation Report for NM_007194.4(CHEK2):c.1011C>A (p.Tyr337Ter)]

NM_007194.4(CHEK2):c.1011C>A (p.Tyr337Ter)

Gene:

CHEK2:checkpoint kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.1

Genomic location:

Preferred name:

NM_007194.4(CHEK2):c.1011C>A (p.Tyr337Ter)

HGVS:

NC_000022.11:g.28696985G>T
NG_008150.2:g.49882C>A
NM_001005735.2:c.1140C>A
NM_001257387.2:c.348C>A
NM_001349956.2:c.810C>A
NM_007194.4:c.1011C>AMANE SELECT
NM_145862.2:c.1009-1112C>A
NP_001005735.1:p.Tyr380Ter
NP_001244316.1:p.Tyr116Ter
NP_001336885.1:p.Tyr270Ter
NP_009125.1:p.Tyr337Ter
LRG_302t1:c.1011C>A
LRG_302:g.49882C>A
LRG_302p1:p.Tyr337Ter
NC_000022.10:g.29092973G>T
NG_008150.1:g.49850C>A
NM_007194.3:c.1011C>A
p.Tyr337*
p.Y337*

Protein change:

Y116*

Links:

dbSNP: rs760502479

NCBI 1000 Genomes Browser:

rs760502479

Molecular consequence:

NM_145862.2:c.1009-1112C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001005735.2:c.1140C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001257387.2:c.348C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001349956.2:c.810C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_007194.4:c.1011C>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus ribosomal protein L22 (Rpl22), transcript variant 2, mRNA
Mus musculus ribosomal protein L22 (Rpl22), transcript variant 2, mRNA
gi|459683844|ref|NM_001277113.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000516126	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 23, 2017)	germline	clinical testing	Citation Link,
SCV000601139	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jul 20, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28152038, 26467025
SCV004225005	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 24, 2023)	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

SCV000516126

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 23, 2017)

germline

clinical testing

Citation Link,

SCV000601139

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jul 20, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004225005

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 24, 2023)

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	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.

LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC.

PLoS One. 2017;12(2):e0170843. doi: 10.1371/journal.pone.0170843.

PubMed [citation]

PMID:: 28152038
PMCID:: PMC5289469

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000516126.5

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

Description

This pathogenic variant is denoted CHEK2 c.1011C>A at the cDNA level and p.Tyr337Ter (Y337X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual undergoing multi-gene panel testing (LaDuca 2017). This variant is considered pathogenic.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601139.2

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

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004225005.1

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

Description

PP5, PM2, PVS1

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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