NM_005026.5(PIK3CD):c.1085A>T (p.Glu362Val) AND Immunodeficiency 14

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 4, 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:: RCV001909392.3

Allele description

NM_005026.5(PIK3CD):c.1085A>T (p.Glu362Val)

Genes:

LOC126805612:MED14-independent group 3 enhancer GRCh37_chr1:9778914-9780113 [Gene]
PIK3CD:phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_005026.5(PIK3CD):c.1085A>T (p.Glu362Val)

HGVS:

NC_000001.11:g.9718758A>T
NG_023434.1:g.72027A>T
NM_001350234.2:c.1085A>T
NM_001350235.1:c.998A>T
NM_005026.5:c.1085A>TMANE SELECT
NP_001337163.1:p.Glu362Val
NP_001337164.1:p.Glu333Val
NP_005017.3:p.Glu362Val
LRG_191:g.72027A>T
NC_000001.10:g.9778816A>T

Protein change:

E333V

Links:

dbSNP: rs1647979472

NCBI 1000 Genomes Browser:

rs1647979472

Molecular consequence:

NM_001350234.2:c.1085A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350235.1:c.998A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005026.5:c.1085A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Immunodeficiency 14 (IMD14A)
Synonyms:: p110-DELTA-ACTIVATING MUTATION CAUSING SENESCENT T CELLS, LYMPHADENOPATHY, AND IMMUNODEFICIENCY; IMMUNODEFICIENCY 14A WITH LYMPHOPROLIFERATION, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0014222; MedGen: C3714976; Orphanet: 397596; OMIM: 615513

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180939	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 4, 2023)	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

SCV002180939

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 4, 2023)

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 Invitae, SCV002180939.3

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

Description

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. 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 expected to disrupt PIK3CD protein function. ClinVar contains an entry for this variant (Variation ID: 1407956). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 362 of the PIK3CD protein (p.Glu362Val).

#	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: Mar 5, 2024

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