NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly) AND Li-Fraumeni syndrome 2

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Mar 6, 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:: RCV001787918.7

Allele description [Variation Report for NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly)]

NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly)

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.349A>G (p.Arg117Gly)

Other names:

p.R117G:AGG>GGG

HGVS:

NC_000022.11:g.28725338T>C
NG_008150.2:g.21529A>G
NM_001005735.2:c.478A>G
NM_001257387.2:c.-429A>G
NM_001349956.2:c.349A>G
NM_007194.4:c.349A>GMANE SELECT
NM_145862.2:c.349A>G
NP_001005735.1:p.Arg160Gly
NP_001336885.1:p.Arg117Gly
NP_009125.1:p.Arg117Gly
NP_665861.1:p.Arg117Gly
LRG_302t1:c.349A>G
LRG_302:g.21529A>G
LRG_302p1:p.Arg117Gly
NC_000022.10:g.29121326T>C
NG_008150.1:g.21497A>G
NM_007194.3:c.349A>G
O96017:p.Arg117Gly
p.(Arg117Gly)
p.R117G

Protein change:

R117G

Links:

UniProtKB: O96017#VAR_022461; dbSNP: rs28909982

NCBI 1000 Genomes Browser:

rs28909982

Molecular consequence:

NM_001257387.2:c.-429A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001005735.2:c.478A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.349A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.349A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.349A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Li-Fraumeni syndrome 2 (TPDS4)
Synonyms:: TUMOR PREDISPOSITION SYNDROME 4; CANCER PREDISPOSITION SYNDROME, CHEK2-RELATED
Identifiers:: MedGen: C5882668; Orphanet: 524; OMIM: 609265

Recent activity

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ovule-2
ovule-2

biosample
actin, partial [Cercospora aff. canescens]
actin, partial [Cercospora aff. canescens]
gi|2314345808|gb|UXX22619.1|

Protein
Absent epiphyses
Absent epiphyses

MedGen
C4021862[conceptid] (1)
MedGen
Chain E, Peptide from Protein numb homolog
Chain E, Peptide from Protein numb homolog
gi|1345621988|pdb|5YQG|E

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002030095	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 25, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003836493	Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	criteria provided, single submitter (Hauer et al. (Genet Med. 2018))	Pathogenic (Mar 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004041663	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Likely pathogenic (Oct 9, 2023)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002030095

Baylor Genetics - CSER-TexasKidsCanSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 25, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003836493

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

criteria provided, single submitter

(Hauer et al. (Genet Med. 2018))

Pathogenic
(Mar 6, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004041663

Zotz-Klimas Genetics Lab, MVZ Zotz Klimas

no assertion criteria provided

Likely pathogenic
(Oct 9, 2023)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature.

Hauer NN, Popp B, Schoeller E, Schuhmann S, Heath KE, Hisado-Oliva A, Klinger P, Kraus C, Trautmann U, Zenker M, Zweier C, Wiesener A, Abou Jamra R, Kunstmann E, Wieczorek D, Uebe S, Ferrazzi F, Büttner C, Ekici AB, Rauch A, Sticht H, Dörr HG, et al.

Genet Med. 2018 Jun;20(6):630-638. doi: 10.1038/gim.2017.159. Epub 2017 Oct 12.

PubMed [citation]

PMID:: 29758562
PMCID:: PMC5993671

Details of each submission

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV002030095.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, SCV003836493.1

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

Description

This variant has been identified by standard clinical testing.

#	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		1	not provided	not provided	not provided

From Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004041663.1

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

#	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

Last Updated: Nov 3, 2024

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