11-17089778-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_002645.4(PIK3C2A):c.5021C>T(p.Thr1674Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002645.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3C2A | ENST00000691414.1 | c.5021C>T | p.Thr1674Met | missense_variant | Exon 33 of 33 | NM_002645.4 | ENSP00000509400.1 | |||
PIK3C2A | ENST00000265970.11 | c.5021C>T | p.Thr1674Met | missense_variant | Exon 32 of 32 | 1 | ENSP00000265970.6 | |||
PIK3C2A | ENST00000531428.1 | n.1400+1556C>T | intron_variant | Intron 12 of 12 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251218Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135778
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461562Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727074
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74276
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.5021C>T (p.T1674M) alteration is located in exon 32 (coding exon 32) of the PIK3C2A gene. This alteration results from a C to T substitution at nucleotide position 5021, causing the threonine (T) at amino acid position 1674 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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. 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. ClinVar contains an entry for this variant (Variation ID: 1930264). This variant has not been reported in the literature in individuals affected with PIK3C2A-related conditions. This variant is present in population databases (rs747006507, gnomAD 0.03%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1674 of the PIK3C2A protein (p.Thr1674Met). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at