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NM_002661.5(PLCG2):c.776C>T (p.Ala259Val) AND Familial cold autoinflammatory syndrome 3

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 16, 2023
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:
RCV003528854.1

Allele description

NM_002661.5(PLCG2):c.776C>T (p.Ala259Val)

Gene:
PLCG2:phospholipase C gamma 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q23.3
Genomic location:
Preferred name:
NM_002661.5(PLCG2):c.776C>T (p.Ala259Val)
HGVS:
  • NC_000016.10:g.81889182C>T
  • NG_032019.2:g.155086C>T
  • NM_001425749.1:c.776C>T
  • NM_001425750.1:c.776C>T
  • NM_001425751.1:c.776C>T
  • NM_002661.5:c.776C>TMANE SELECT
  • NP_001412678.1:p.Ala259Val
  • NP_001412679.1:p.Ala259Val
  • NP_001412680.1:p.Ala259Val
  • NP_002652.2:p.Ala259Val
  • NP_002652.2:p.Ala259Val
  • LRG_376t1:c.776C>T
  • LRG_376:g.155086C>T
  • LRG_376p1:p.Ala259Val
  • NC_000016.9:g.81922787C>T
  • NM_002661.3:c.776C>T
Protein change:
A259V
Molecular consequence:
  • NM_001425749.1:c.776C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001425750.1:c.776C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001425751.1:c.776C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002661.5:c.776C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cold autoinflammatory syndrome 3 (FCAS3)
Synonyms:
FAMILIAL ATYPICAL COLD URTICARIA; ANTIBODY DEFICIENCY AND IMMUNE DYSREGULATION, PLCG2-ASSOCIATED
Identifiers:
MONDO: MONDO:0013766; MedGen: C3280914; Orphanet: 300359; OMIM: 614468

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004366542Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 16, 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 Invitae, SCV004366542.1

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 259 of the PLCG2 protein (p.Ala259Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PLCG2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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: Sep 1, 2024