chr8-68055931-C-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_024870.4(PREX2):c.1195C>A(p.Arg399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 1,607,770 control chromosomes in the GnomAD database, including 216,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.59 ( 28181 hom., cov: 32)
Exomes 𝑓: 0.50 ( 188248 hom. )
Consequence
PREX2
NM_024870.4 synonymous
NM_024870.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.56
Genes affected
PREX2 (HGNC:22950): (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2) The protein encoded by this gene belongs to the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger (PREX) family, which are Dbl-type guanine-nucleotide exchange factors for Rac family small G proteins. Structural domains of this protein include the catalytic diffuse B-cell lymphoma homology and pleckstrin homology (DHPH) domain, two disheveled, EGL-10, and pleckstrin homology (DEP) domains, two PDZ domains, and a C-terminal inositol polyphosphate-4 phosphatase (IP4P) domain that is found in one of the isoforms. This protein facilitates the exchange of GDP for GTP on Rac1, allowing the GTP-bound Rac1 to activate downstream effectors. Studies also show that the pleckstrin homology domain of this protein interacts with the phosphatase and tensin homolog (PTEN) gene product to inhibit PTEN phosphatase activity, thus activating the phosphoinositide-3 kinase (PI3K) signaling pathway. Conversely, the PTEN gene product has also been shown to inhibit the GEF activity of this protein. This gene plays a role in insulin-signaling pathways, and either mutations or overexpression of this gene have been observed in some cancers. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 8-68055931-C-A is Benign according to our data. Variant chr8-68055931-C-A is described in ClinVar as [Benign]. Clinvar id is 1274701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PREX2 | NM_024870.4 | c.1195C>A | p.Arg399= | synonymous_variant | 10/40 | ENST00000288368.5 | |
PREX2 | NM_025170.6 | c.1195C>A | p.Arg399= | synonymous_variant | 10/24 | ||
PREX2 | XM_047422267.1 | c.1060C>A | p.Arg354= | synonymous_variant | 10/40 | ||
PREX2 | XM_047422268.1 | c.1195C>A | p.Arg399= | synonymous_variant | 10/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PREX2 | ENST00000288368.5 | c.1195C>A | p.Arg399= | synonymous_variant | 10/40 | 1 | NM_024870.4 | P1 | |
PREX2 | ENST00000529398.5 | n.1222C>A | non_coding_transcript_exon_variant | 10/24 | 1 | ||||
PREX2 | ENST00000517617.1 | n.906C>A | non_coding_transcript_exon_variant | 8/24 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.588 AC: 89063AN: 151438Hom.: 28127 Cov.: 32
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GnomAD3 exomes AF: 0.497 AC: 124000AN: 249518Hom.: 32821 AF XY: 0.493 AC XY: 66497AN XY: 134812
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GnomAD4 exome AF: 0.502 AC: 731017AN: 1456214Hom.: 188248 Cov.: 34 AF XY: 0.501 AC XY: 363000AN XY: 724554
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
PREX2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 43
Find out detailed SpliceAI scores and Pangolin per-transcript scores at