rs2327225

Positions:

• chr20-9767480-C-A

Variant summary

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

The ENST00000353224.10(PAK5):​c.-161-56045G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,122 control chromosomes in the GnomAD database, including 46,246 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 0.78 (46246 hom., cov: 32)
• Consequence: PAK5 ENST00000353224.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-161-56045G>T		intron_variant		ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-161-56045G>T		intron_variant		1	NM_177990.4	ENSP00000322957	P1
PAK5	ENST00000378423.5	c.-162+16878G>T		intron_variant		1		ENSP00000367679	P1
PAK5	ENST00000378429.3	c.-162+51200G>T		intron_variant		1		ENSP00000367686	P1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118136 AN: 152004 Hom.: 46199 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.777 AC: 118235 AN: 152122 Hom.: 46246 Cov.: 32 AF XY: 0.776 AC XY: 57701 AN XY: 74348

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.779

Alfa AF: 0.738 Hom.: 53997

Bravo AF: 0.784

Asia WGS AF: 0.788 AC: 2741 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	0.013
DANN	Benign	0.21

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: rs2327225; hg19: chr20-9748128;