NM_007194.4(CHEK2):c.962A>C (p.Glu321Ala) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: May 16, 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:: RCV000522320.28

Allele description [Variation Report for NM_007194.4(CHEK2):c.962A>C (p.Glu321Ala)]

NM_007194.4(CHEK2):c.962A>C (p.Glu321Ala)

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.962A>C (p.Glu321Ala)

HGVS:

NC_000022.11:g.28699884T>G
NG_008150.2:g.46983A>C
NM_001005735.2:c.1091A>C
NM_001257387.2:c.299A>C
NM_001349956.2:c.761A>C
NM_007194.4:c.962A>CMANE SELECT
NM_145862.2:c.962A>C
NP_001005735.1:p.Glu364Ala
NP_001244316.1:p.Glu100Ala
NP_001336885.1:p.Glu254Ala
NP_009125.1:p.Glu321Ala
NP_665861.1:p.Glu321Ala
LRG_302t1:c.962A>C
LRG_302:g.46983A>C
LRG_302p1:p.Glu321Ala
NC_000022.10:g.29095872T>G
NG_008150.1:g.46951A>C
NM_007194.3:c.962A>C

Protein change:

E100A

Links:

dbSNP: rs374395284

NCBI 1000 Genomes Browser:

rs374395284

Molecular consequence:

NM_001005735.2:c.1091A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001257387.2:c.299A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349956.2:c.761A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007194.4:c.962A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_145862.2:c.962A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000618399	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 16, 2024)	germline	clinical testing	Citation Link,
SCV001134176	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 20, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002064091	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Nov 1, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000618399

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 16, 2024)

germline

clinical testing

Citation Link,

SCV001134176

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jun 20, 2019)

germline

clinical testing

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

SCV002064091

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Nov 1, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

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

Details of each submission

From GeneDx, SCV000618399.5

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.1091A>C p.(E364A); This variant is associated with the following publications: (PMID: 31398194, 35264596, 19782031, 22419737, 35534704, 38367672)

#	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, SCV001134176.2

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

#	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 CeGaT Center for Human Genetics Tuebingen, SCV002064091.20

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

Last Updated: Oct 20, 2024

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