5-68226877-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS1_Supporting
The NM_181523.3(PIK3R1):c.202G>A(p.Asp68Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D68H) has been classified as Uncertain significance.
Frequency
Consequence
NM_181523.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.202G>A | p.Asp68Asn | missense_variant | 2/16 | ENST00000521381.6 | |
PIK3R1 | XM_005248542.4 | c.202G>A | p.Asp68Asn | missense_variant | 2/16 | ||
PIK3R1 | XM_017009585.3 | c.202G>A | p.Asp68Asn | missense_variant | 2/16 | ||
PIK3R1 | XM_047417315.1 | c.202G>A | p.Asp68Asn | missense_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.202G>A | p.Asp68Asn | missense_variant | 2/16 | 1 | NM_181523.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250954Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727228
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PIK3R1-related disease. This variant is present in population databases (rs755043940, ExAC 0.009%). This sequence change replaces aspartic acid with asparagine at codon 68 of the PIK3R1 protein (p.Asp68Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at