rs843530

chr3-196754153-T-C

Variant summary

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

The NM_002577.4(PAK2):c.-22+13996T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,984 control chromosomes in the GnomAD database, including 16,967 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 0.47 (16967 hom., cov: 32)
• Consequence: PAK2 NM_002577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK2	NM_002577.4	c.-22+13996T>C		intron_variant		ENST00000327134.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK2	ENST00000327134.7	c.-22+13996T>C		intron_variant		2	NM_002577.4	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70802 AN: 151870 Hom.: 16957 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.466 AC: 70838 AN: 151984 Hom.: 16967 Cov.: 32 AF XY: 0.464 AC XY: 34479 AN XY: 74282

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.435

Alfa AF: 0.495 Hom.: 3595

Bravo AF: 0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs843530; hg19: chr3-196481024;