8-68038151-TGACTTAG-T

Variant names:

• chr8-68038151-TGACTTAG-T
• NM_024870.4:c.706-6_706delACTTAGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024870.4(PREX2):​c.706-6_706delACTTAGG​(p.Ser237fs) variant causes a frameshift, splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PREX2 NM_024870.4 frameshift, splice_acceptor, splice_region, intron
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 9.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREX2	NM_024870.4	c.706-6_706delACTTAGG	p.Ser237fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 7 of 40	ENST00000288368.5	NP_079146.2
PREX2	NM_025170.6	c.706-6_706delACTTAGG	p.Ser237fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 7 of 24		NP_079446.3
PREX2	XM_047422267.1	c.571-6_571delACTTAGG	p.Ser192fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 7 of 40		XP_047278223.1
PREX2	XM_047422268.1	c.706-6_706delACTTAGG	p.Ser237fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 7 of 28		XP_047278224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX2	ENST00000288368.5	c.706-7_706-1delGACTTAG		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 6 of 39	1	NM_024870.4	ENSP00000288368.4
PREX2	ENST00000529398.5	n.733-7_733-1delGACTTAG		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 6 of 23	1
PREX2	ENST00000517617.1	n.417-7_417-1delGACTTAG		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 4 of 23	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: -

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-68950386;