rs6789365

Positions:

• chr3-196828081-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002577.4(PAK2):​c.1489-238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 96,220 control chromosomes in the GnomAD database, including 1,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (1322 hom., cov: 25)
• Consequence: PAK2 NM_002577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.99

Genes affected

PAK2 (HGNC:8591): (p21 (RAC1) activated kinase 2) The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK2	NM_002577.4	c.1489-238C>A		intron_variant		ENST00000327134.7	NP_002568.2
PAK2	XM_011512870.3	c.1489-238C>A		intron_variant			XP_011511172.1
PAK2	XM_047448218.1	c.1489-238C>A		intron_variant			XP_047304174.1
PAK2	XM_047448219.1	c.1489-238C>A		intron_variant			XP_047304175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK2	ENST00000327134.7	c.1489-238C>A		intron_variant		2	NM_002577.4	ENSP00000314067.3
PAK2	ENST00000426668.1	c.577-238C>A		intron_variant		3		ENSP00000402927.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 7607 AN: 96144 Hom.: 1317 Cov.: 25

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00610

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0681

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

GnomAD4 genome AF: 0.0792 AC: 7621 AN: 96220 Hom.: 1322 Cov.: 25 AF XY: 0.0809 AC XY: 3789 AN XY: 46838

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.0719

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.214 Hom.: 3465

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6789365; hg19: chr3-196554952; COSMIC: COSV59079080;