rs2423422

Variant names:

• chr20-9691426-A-C
• rs2423422
• NM_177990.4:c.-12+19860T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.82).
• 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 rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-12+19860T>G		intron_variant	Intron 2 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-12+19860T>G		intron_variant	Intron 2 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.-12+19860T>G		intron_variant	Intron 3 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.-12+19860T>G		intron_variant	Intron 3 of 10	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

African (AFR) AF: 0.575 AC: 23844 AN: 41448

American (AMR) AF: 0.317 AC: 4849 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1894 AN: 5150

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2647 AN: 10600

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16118 AN: 67976

Other (OTH) AF: 0.308 AC: 651 AN: 2114

Alfa AF: 0.205 Hom.: 756

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
PhyloP100		1.5
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: rs2423422; hg19: chr20-9672074;