3-196826996-A-G

Variant names:

• chr3-196826996-A-G
• rs2084385
• NM_002577.4:c.1351-200A>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.1351-200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,130 control chromosomes in the GnomAD database, including 59,220 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 0.88 (59220 hom., cov: 31)
• Consequence: PAK2 NM_002577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK2	NM_002577.4	MANE Select	c.1351-200A>G		intron	N/A	NP_002568.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK2	ENST00000327134.7	TSL:2 MANE Select	c.1351-200A>G		intron	N/A	ENSP00000314067.3
	PAK2	ENST00000426668.1	TSL:3	c.577-1323A>G		intron	N/A	ENSP00000402927.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133994 AN: 152012 Hom.: 59158 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.882 AC: 134117 AN: 152130 Hom.: 59220 Cov.: 31 AF XY: 0.880 AC XY: 65417 AN XY: 74344

African (AFR) AF: 0.880 AC: 36542 AN: 41506

American (AMR) AF: 0.912 AC: 13939 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3004 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5181 AN: 5184

South Asian (SAS) AF: 0.888 AC: 4280 AN: 4822

European-Finnish (FIN) AF: 0.807 AC: 8497 AN: 10526

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59666 AN: 68016

Other (OTH) AF: 0.886 AC: 1873 AN: 2114

Alfa AF: 0.883 Hom.: 138163

Bravo AF: 0.890

Asia WGS AF: 0.948 AC: 3293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.93
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: rs2084385; hg19: chr3-196553867;