chr11-17089753-C-T
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The NM_002645.4(PIK3C2A):c.5046G>A(p.Ala1682=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,612,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
PIK3C2A
NM_002645.4 synonymous
NM_002645.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0500
Genes affected
PIK3C2A (HGNC:8971): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 11-17089753-C-T is Benign according to our data. Variant chr11-17089753-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2164260.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.05 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000658 (10/152088) while in subpopulation SAS AF= 0.000207 (1/4828). AF 95% confidence interval is 0.0000325. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3C2A | NM_002645.4 | c.5046G>A | p.Ala1682= | synonymous_variant | 33/33 | ENST00000691414.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3C2A | ENST00000691414.1 | c.5046G>A | p.Ala1682= | synonymous_variant | 33/33 | NM_002645.4 | P1 | ||
PIK3C2A | ENST00000265970.11 | c.5046G>A | p.Ala1682= | synonymous_variant | 32/32 | 1 | P1 | ||
PIK3C2A | ENST00000531428.1 | n.1400+1581G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152088Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000800 AC: 20AN: 250138Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135206
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GnomAD4 exome AF: 0.000178 AC: 260AN: 1460066Hom.: 0 Cov.: 30 AF XY: 0.000186 AC XY: 135AN XY: 726288
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GnomAD4 genome AF: 0.0000658 AC: 10AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74272
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 03, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at