20-9608930-T-C

Variant names:

• chr20-9608930-T-C
• rs2225471
• NM_177990.4:c.205-28000A>G

Variant summary

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

The NM_177990.4(PAK5):​c.205-28000A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,110 control chromosomes in the GnomAD database, including 25,336 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 0.56 (25336 hom., cov: 33)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK5	NM_177990.4	MANE Select	c.205-28000A>G		intron	N/A	NP_817127.1	Q9P286
	PAK5	NM_020341.5		c.205-28000A>G		intron	N/A	NP_065074.1	Q9P286

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK5	ENST00000353224.10	TSL:1 MANE Select	c.205-28000A>G		intron	N/A	ENSP00000322957.5	Q9P286
	PAK5	ENST00000378423.5	TSL:1	c.205-28000A>G		intron	N/A	ENSP00000367679.1	Q9P286
	PAK5	ENST00000378429.3	TSL:1	c.205-28000A>G		intron	N/A	ENSP00000367686.3	Q9P286

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84515 AN: 151992 Hom.: 25286 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.556 AC: 84623 AN: 152110 Hom.: 25336 Cov.: 33 AF XY: 0.551 AC XY: 40951 AN XY: 74336

African (AFR) AF: 0.789 AC: 32767 AN: 41550

American (AMR) AF: 0.512 AC: 7822 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1692 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2698 AN: 5152

South Asian (SAS) AF: 0.325 AC: 1564 AN: 4814

European-Finnish (FIN) AF: 0.458 AC: 4842 AN: 10570

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31526 AN: 67946

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.449 Hom.: 7444

Bravo AF: 0.575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.27
PhyloP100		0.017
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: rs2225471; hg19: chr20-9589577;