dbSNP rs6789365: PAK2:c.1489-238C>A (chr3-196828081-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.99

Publications

3 publications found

Variant links:

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

PAK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PAK2	NM_002577.4 link	c.1489-238C>A	intron_variant	Intron 14 of 14	ENST00000327134.7	NP_002568.2
PAK2	XM_011512870.3 link	c.1489-238C>A	intron_variant	Intron 14 of 14		XP_011511172.1
PAK2	XM_047448218.1 link	c.1489-238C>A	intron_variant	Intron 14 of 14		XP_047304174.1
PAK2	XM_047448219.1 link	c.1489-238C>A	intron_variant	Intron 14 of 14		XP_047304175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK2	ENST00000327134.7 link	c.1489-238C>A		intron_variant	Intron 14 of 14	2	NM_002577.4	ENSP00000314067.3
PAK2	ENST00000426668.1 link	c.577-238C>A		intron_variant	Intron 5 of 5	3		ENSP00000402927.1

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

7607

AN:

96144

Hom.:

1317

Cov.:

show subpopulations

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.:

AF XY:

0.0809

AC XY:

3789

AN XY:

46838

show subpopulations

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:

AN:

164

European-Non Finnish (NFE)

AF:

0.0505

AC:

2454

AN:

48632

Other (OTH)

AF:

0.0664

AC:

AN:

1280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

221

443

664

886

1107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.223

Hom.:

5099

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over