rs2423467

Variant names:

• chr20-9761228-A-G
• rs2423467
• NM_177990.4:c.-161-49793T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-9761228-A-G
• chr20-9761228-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.-161-49793T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,868 control chromosomes in the GnomAD database, including 12,311 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 0.39 (12311 hom., cov: 31)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-161-49793T>C		intron_variant	Intron 1 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-161-49793T>C		intron_variant	Intron 1 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.-162+23130T>C		intron_variant	Intron 2 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.-161-49793T>C		intron_variant	Intron 2 of 10	1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59484 AN: 151752 Hom.: 12280 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.392 AC: 59570 AN: 151868 Hom.: 12311 Cov.: 31 AF XY: 0.399 AC XY: 29656 AN XY: 74248

African (AFR) AF: 0.465 AC: 19243 AN: 41406

American (AMR) AF: 0.504 AC: 7691 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2955 AN: 5148

South Asian (SAS) AF: 0.375 AC: 1801 AN: 4806

European-Finnish (FIN) AF: 0.408 AC: 4315 AN: 10566

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21406 AN: 67912

Other (OTH) AF: 0.372 AC: 783 AN: 2106

Alfa AF: 0.345 Hom.: 40652

Bravo AF: 0.407

Asia WGS AF: 0.473 AC: 1643 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	4.7
DANN	Benign	0.83
PhyloP100		-0.0070
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: rs2423467; hg19: chr20-9741876;