3-196803029-C-G

Position:

• chr3-196803029-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002577.4(PAK2):​c.301C>G​(p.Gln101Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAK2 NM_002577.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK2	NM_002577.4	c.301C>G	p.Gln101Glu	missense_variant	4/15	ENST00000327134.7	NP_002568.2
PAK2	XM_011512870.3	c.301C>G	p.Gln101Glu	missense_variant	4/15		XP_011511172.1
PAK2	XM_047448218.1	c.301C>G	p.Gln101Glu	missense_variant	4/15		XP_047304174.1
PAK2	XM_047448219.1	c.301C>G	p.Gln101Glu	missense_variant	4/15		XP_047304175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK2	ENST00000327134.7	c.301C>G	p.Gln101Glu	missense_variant	4/15	2	NM_002577.4	ENSP00000314067.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.301C>G (p.Q101E) alteration is located in exon 4 (coding exon 3) of the PAK2 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the glutamine (Q) at amino acid position 101 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.87
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.32	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.47
Sift	Benign	0.56	T
Sift4G	Benign	1.0	T
Polyphen		0.012	B
Vest4		0.80
MutPred		0.54		Gain of helix (P = 0.0078);
MVP		0.87
MPC		0.99
ClinPred		0.53	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-196529900;