chr3-196798707-A-G

Variant names:

• chr3-196798707-A-G
• rs6583176
• NM_002577.4:c.188-3220A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002577.4(PAK2):​c.188-3220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,174 control chromosomes in the GnomAD database, including 51,880 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 0.82 (51880 hom., cov: 31)
• Consequence: PAK2 NM_002577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75
• Publications: 12 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK2	NM_002577.4	c.188-3220A>G		intron_variant	Intron 2 of 14	ENST00000327134.7	NP_002568.2
PAK2	XM_011512870.3	c.188-3220A>G		intron_variant	Intron 2 of 14		XP_011511172.1
PAK2	XM_047448218.1	c.188-3220A>G		intron_variant	Intron 2 of 14		XP_047304174.1
PAK2	XM_047448219.1	c.188-3220A>G		intron_variant	Intron 2 of 14		XP_047304175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK2	ENST00000327134.7	c.188-3220A>G		intron_variant	Intron 2 of 14	2	NM_002577.4	ENSP00000314067.3

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125264 AN: 152056 Hom.: 51837 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.824 AC: 125366 AN: 152174 Hom.: 51880 Cov.: 31 AF XY: 0.825 AC XY: 61341 AN XY: 74396

African (AFR) AF: 0.878 AC: 36440 AN: 41516

American (AMR) AF: 0.850 AC: 12977 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2503 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3634 AN: 5170

South Asian (SAS) AF: 0.729 AC: 3513 AN: 4816

European-Finnish (FIN) AF: 0.869 AC: 9203 AN: 10596

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54439 AN: 68010

Other (OTH) AF: 0.784 AC: 1657 AN: 2114

Alfa AF: 0.804 Hom.: 47584

Bravo AF: 0.828

Asia WGS AF: 0.695 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.24
PhyloP100		-3.8
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: rs6583176; hg19: chr3-196525578;