NM_001370466.1(NOD2):c.1434del (p.Ser479fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 1, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002547164.10

Allele description [Variation Report for NM_001370466.1(NOD2):c.1434del (p.Ser479fs)]

NM_001370466.1(NOD2):c.1434del (p.Ser479fs)

Gene:

NOD2:nucleotide binding oligomerization domain containing 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001370466.1(NOD2):c.1434del (p.Ser479fs)

HGVS:

NC_000016.10:g.50711426del
NG_007508.1:g.19288del
NM_001293557.2:c.1434del
NM_001370466.1:c.1434delMANE SELECT
NM_022162.2:c.1509delG
NM_022162.3:c.1515del
NP_001280486.1:p.Ser479fs
NP_001357395.1:p.Ser479fs
NP_071445.1:p.Ser506fs
LRG_177:g.19288del
NC_000016.9:g.50745331del
NC_000016.9:g.50745337del
NM_022162.2:c.1509delG
NM_022162.2:c.1515delG
NR_163434.1:n.1499del

Protein change:

S479fs

Links:

dbSNP: rs754761524

NCBI 1000 Genomes Browser:

rs754761524

Molecular consequence:

NM_001293557.2:c.1434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370466.1:c.1434del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022162.3:c.1515del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_163434.1:n.1499del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Blau syndrome (BLAUS)
Synonyms:: Synovitis granulomatous with uveitis and cranial neuropathies; Arthrocutaneouveal granulomatosis; Granulomatosis, familial, Blau type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008523; MedGen: C5201146; Orphanet: 90340; OMIM: 186580

Name:: Regional enteritis
Synonyms:: Enteritis, Granulomatous
Identifiers:: MeSH: D003424; MedGen: C0678202

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sterile alpha motif domain-containing protein 9 [Homo sapiens]
sterile alpha motif domain-containing protein 9 [Homo sapiens]
gi|300863105|ref|NP_001180236.1|

Protein
Profile neighbors for GEO Profiles (Select 131668384) (199)
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Chromosome neighbors for GEO Profiles (Select 132351861) (20)
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Chromosome neighbors for GEO Profiles (Select 132341852) (20)
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Chromosome neighbors for GEO Profiles (Select 131697690) (20)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000818891	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	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

SCV000818891

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000818891.7

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

Description

This sequence change creates a premature translational stop signal (p.Ser506Profs*11) in the NOD2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NOD2 cause disease. This variant is present in population databases (rs767278572, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 570310). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Nov 3, 2024

ClinVar

Relating variation to medicine