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NM_024408.4(NOTCH2):c.7223T>A (p.Leu2408His)

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Interpretation:
Benign/Likely benign​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Sep 27, 2021)
Last evaluated:
Jan 21, 2021
Accession:
VCV000134987.4
Variation ID:
134987
Description:
single nucleotide variant
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NM_024408.4(NOTCH2):c.7223T>A (p.Leu2408His)

Allele ID
138726
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p12
Genomic location
1: 119915499 (GRCh38) GRCh38 UCSC
1: 120458122 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.120458122A>T
NC_000001.11:g.119915499A>T
NG_008163.1:g.159155T>A
NM_024408.4:c.7223T>A MANE Select NP_077719.2:p.Leu2408His missense
Protein change
L2408H
Other names
-
Canonical SPDI
NC_000001.11:119915498:A:T
Functional consequence
variation affecting RNA [Variation Ontology VariO:0297]
Global minor allele frequency (GMAF)
0.00080 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00179
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00208
Trans-Omics for Precision Medicine (TOPMed) 0.00209
1000 Genomes Project 0.00080
The Genome Aggregation Database (gnomAD) 0.00236
Links
ClinGen: CA161301
dbSNP: rs35586704
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 3 criteria provided, multiple submitters, no conflicts Feb 5, 2016 RCV000121737.3
Likely benign 1 criteria provided, single submitter Dec 31, 2019 RCV000540032.4
Benign 1 criteria provided, single submitter Jan 21, 2021 RCV001711395.1
Uncertain significance 1 no assertion criteria provided Nov 18, 2016 RCV000508681.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
NOTCH2 No evidence available No evidence available GRCh38
GRCh37
490 512

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Feb 05, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000339428.4
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely benign
(Dec 31, 2019)
criteria provided, single submitter
Method: clinical testing
Hajdu-Cheney syndrome
Allele origin: germline
Invitae
Accession: SCV000636912.4
Submitted: (Jan 29, 2020)
Evidence details
Benign
(Jan 21, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001942685.1
Submitted: (Sep 27, 2021)
Evidence details
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in possible association with primary … (more)
Likely benign
(Dec 17, 2015)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: unknown
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia
Accession: SCV000297311.2
Submitted: (Jan 06, 2016)
Evidence details
Uncertain significance
(Nov 18, 2016)
no assertion criteria provided
Method: clinical testing
Hirschsprung disease 1
(Oligogenic inheritance)
Allele origin: germline
Clinical Genetics, Erasmus University Medical Center
Accession: SCV000328906.1
Submitted: (Nov 21, 2016)
Evidence details
not provided
(Sep 19, 2013)
no assertion provided
Method: reference population
AllHighlyPenetrant
Allele origin: germline
ITMI
Accession: SCV000085935.1
Submitted: (May 29, 2014)
Comment:
Please see associated publication for description of ethnicities
Evidence details
Publications
PubMed (1)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
variation affecting RNA
Clinical Genetics, Erasmus University Medical Center
Accession: SCV000328906.1
Submitted: (Nov 21, 2016)
Evidence details

Citations for this variant

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Title Author Journal Year Link
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. Bodian DL PloS one 2014 PMID: 24728327
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NOTCH2 - - - -

Text-mined citations for rs35586704...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 02, 2021