rs2072952

Variant names:

• chr20-9544954-T-C
• rs2072952
• NM_177990.4:c.1744-460A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-9544954-T-C
• chr20-9544954-T-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.1744-460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,064 control chromosomes in the GnomAD database, including 19,424 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 0.45 (19424 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.1744-460A>G		intron_variant	Intron 7 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.1744-460A>G		intron_variant	Intron 7 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.1744-460A>G		intron_variant	Intron 8 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.1744-460A>G		intron_variant	Intron 8 of 10	1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69068 AN: 151948 Hom.: 19366 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.455 AC: 69185 AN: 152064 Hom.: 19424 Cov.: 32 AF XY: 0.454 AC XY: 33750 AN XY: 74334

African (AFR) AF: 0.798 AC: 33076 AN: 41470

American (AMR) AF: 0.374 AC: 5715 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3468

East Asian (EAS) AF: 0.569 AC: 2944 AN: 5178

South Asian (SAS) AF: 0.316 AC: 1518 AN: 4810

European-Finnish (FIN) AF: 0.292 AC: 3090 AN: 10584

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.296 AC: 20132 AN: 67970

Other (OTH) AF: 0.440 AC: 929 AN: 2112

Alfa AF: 0.336 Hom.: 15583

Bravo AF: 0.481

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.49
DANN	Benign	0.53
PhyloP100		-0.32
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: rs2072952; hg19: chr20-9525601;