NM_001370466.1(NOD2):c.1058G>A (p.Gly353Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 2019
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:: RCV001040250.2

Allele description [Variation Report for NM_001370466.1(NOD2):c.1058G>A (p.Gly353Asp)]

NM_001370466.1(NOD2):c.1058G>A (p.Gly353Asp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001370466.1(NOD2):c.1058G>A (p.Gly353Asp)

HGVS:

NC_000016.10:g.50711050G>A
NG_007508.1:g.18912G>A
NM_001293557.2:c.1058G>A
NM_001370466.1:c.1058G>AMANE SELECT
NM_022162.3:c.1139G>A
NP_001280486.1:p.Gly353Asp
NP_001357395.1:p.Gly353Asp
NP_071445.1:p.Gly380Asp
LRG_177:g.18912G>A
NC_000016.9:g.50744961G>A
NM_022162.2:c.1139G>A
NR_163434.1:n.1123G>A

Protein change:

G353D

Links:

dbSNP: rs1964456255

NCBI 1000 Genomes Browser:

rs1964456255

Molecular consequence:

NM_001293557.2:c.1058G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1058G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1139G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1123G>A - 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:: Inflammatory bowel disease 1 (IBD1)
Synonyms:: Inflammatory bowel disease 1, Crohn disease; INFLAMMATORY BOWEL DISEASE (CROHN DISEASE) 1
Identifiers:: MONDO: MONDO:0009960; MedGen: CN260071; OMIM: 266600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001203812	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 27, 2019)	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

SCV001203812

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 27, 2019)

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, SCV001203812.1

#	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 replaces glycine with aspartic acid at codon 380 of the NOD2 protein (p.Gly380Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NOD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Sep 29, 2024

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