rs545136223
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS1_Supporting
The NM_005026.5(PIK3CD):c.1513G>A(p.Glu505Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000377 in 1,537,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005026.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3CD | NM_005026.5 | c.1513G>A | p.Glu505Lys | missense_variant | 12/24 | ENST00000377346.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CD | ENST00000377346.9 | c.1513G>A | p.Glu505Lys | missense_variant | 12/24 | 1 | NM_005026.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000113 AC: 17AN: 149924Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000626 AC: 9AN: 143672Hom.: 0 AF XY: 0.0000260 AC XY: 2AN XY: 77068
GnomAD4 exome AF: 0.0000295 AC: 41AN: 1387500Hom.: 0 Cov.: 52 AF XY: 0.0000263 AC XY: 18AN XY: 684468
GnomAD4 genome ? AF: 0.000113 AC: 17AN: 150036Hom.: 0 Cov.: 29 AF XY: 0.0000819 AC XY: 6AN XY: 73218
ClinVar
Submissions by phenotype
Immunodeficiency 14 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2023 | 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 not expected to disrupt PIK3CD protein function. ClinVar contains an entry for this variant (Variation ID: 541087). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. This variant is present in population databases (rs545136223, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 505 of the PIK3CD protein (p.Glu505Lys). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.1513G>A (p.E505K) alteration is located in exon 12 (coding exon 10) of the PIK3CD gene. This alteration results from a G to A substitution at nucleotide position 1513, causing the glutamic acid (E) at amino acid position 505 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at