U.S. flag

An official website of the United States government

NM_144687.4(NLRP12):c.986G>A (p.Arg329Gln) AND Familial cold autoinflammatory syndrome 2

Germline classification:
Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:
Dec 11, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000264278.15

Allele description [Variation Report for NM_144687.4(NLRP12):c.986G>A (p.Arg329Gln)]

NM_144687.4(NLRP12):c.986G>A (p.Arg329Gln)

Gene:
NLRP12:NLR family pyrin domain containing 12 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.42
Genomic location:
Preferred name:
NM_144687.4(NLRP12):c.986G>A (p.Arg329Gln)
HGVS:
  • NC_000019.10:g.53810673C>T
  • NG_008651.2:g.18722G>A
  • NM_001277126.2:c.986G>A
  • NM_001277129.1:c.986G>A
  • NM_144687.2:c.986G>A
  • NM_144687.4:c.986G>AMANE SELECT
  • NP_001264055.1:p.Arg329Gln
  • NP_001264058.1:p.Arg329Gln
  • NP_653288.1:p.Arg329Gln
  • NP_653288.1:p.Arg329Gln
  • LRG_181t1:c.986G>A
  • LRG_181t2:c.986G>A
  • LRG_181:g.18722G>A
  • LRG_181p1:p.Arg329Gln
  • LRG_181p2:p.Arg329Gln
  • NC_000019.9:g.54313927C>T
  • NG_008651.1:g.18722G>A
  • NM_144687.3:c.986G>A
Protein change:
R329Q
Links:
dbSNP: rs144287432
NCBI 1000 Genomes Browser:
rs144287432
Molecular consequence:
  • NM_001277126.2:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001277129.1:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_144687.4:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cold autoinflammatory syndrome 2 (FCAS2)
Identifiers:
MONDO: MONDO:0012724; MedGen: C2673198; Orphanet: 247868; OMIM: 611762

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000414550Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)		Likely benign
(Jan 13, 2018) 		germlineclinical testing

Citation Link,

SCV001409048Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 11, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Illumina Laboratory Services, Illumina, SCV000414550.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001409048.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 329 of the NLRP12 protein (p.Arg329Gln). This variant is present in population databases (rs144287432, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 330033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NLRP12 protein function with a negative predictive value of 80%. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 19, 2025