rs2423422

Positions:

• chr20-9691426-A-C
• chr20-9691426-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177990.4(PAK5):​c.-12+19860T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,070 control chromosomes in the GnomAD database, including 10,752 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 0.35 (10752 hom., cov: 31)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

PAK5 (HGNC:15916): (p21 (RAC1) activated kinase 5) The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP. This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-12+19860T>G		intron_variant		ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-12+19860T>G		intron_variant		1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.-12+19860T>G		intron_variant		1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.-12+19860T>G		intron_variant		1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52385 AN: 151952 Hom.: 10726 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.345 AC: 52467 AN: 152070 Hom.: 10752 Cov.: 31 AF XY: 0.345 AC XY: 25638 AN XY: 74346

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.308

Alfa AF: 0.192 Hom.: 617

Bravo AF: 0.363

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs2423422; hg19: chr20-9672074;