rs6789365

Variant names:

• chr3-196828081-C-A
• rs6789365
• NM_002577.4:c.1489-238C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PAK2 Gene-Disease associations (from GenCC):

• Knobloch syndrome 2

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK2	NM_002577.4	MANE Select	c.1489-238C>A		intron	N/A	NP_002568.2	Q13177

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK2	ENST00000327134.7	TSL:2 MANE Select	c.1489-238C>A		intron	N/A	ENSP00000314067.3	Q13177
	PAK2	ENST00000871388.1		c.1489-238C>A		intron	N/A	ENSP00000541447.1
	PAK2	ENST00000871391.1		c.1489-238C>A		intron	N/A	ENSP00000541450.1

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

African (AFR) AF: 0.158 AC: 3198 AN: 20300

American (AMR) AF: 0.0841 AC: 706 AN: 8392

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 157 AN: 2424

East Asian (EAS) AF: 0.0719 AC: 264 AN: 3674

South Asian (SAS) AF: 0.0710 AC: 233 AN: 3282

European-Finnish (FIN) AF: 0.0688 AC: 499 AN: 7252

Middle Eastern (MID) AF: 0.122 AC: 20 AN: 164

European-Non Finnish (NFE) AF: 0.0505 AC: 2454 AN: 48632

Other (OTH) AF: 0.0664 AC: 85 AN: 1280

Alfa AF: 0.223 Hom.: 5099

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.64
PhyloP100		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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