rs843530

Variant names:

• chr3-196754153-T-C
• rs843530
• NM_002577.4:c.-22+13996T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 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.-22+13996T>C		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.-22+13996T>C		intron	N/A	ENSP00000314067.3	Q13177
	PAK2	ENST00000871388.1		c.-140-11768T>C		intron	N/A	ENSP00000541447.1
	PAK2	ENST00000871391.1		c.-208-11768T>C		intron	N/A	ENSP00000541450.1

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

African (AFR) AF: 0.393 AC: 16282 AN: 41428

American (AMR) AF: 0.416 AC: 6362 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1301 AN: 5176

South Asian (SAS) AF: 0.425 AC: 2046 AN: 4818

European-Finnish (FIN) AF: 0.549 AC: 5782 AN: 10538

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36259 AN: 67960

Other (OTH) AF: 0.435 AC: 917 AN: 2108

Alfa AF: 0.492 Hom.: 3661

Bravo AF: 0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs843530; hg19: chr3-196481024;