rs2844337

Positions:

• chr11-77322663-A-C
• chr11-77322663-A-G

Variant summary

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

The NM_002576.5(PAK1):​c.*611T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 242,172 control chromosomes in the GnomAD database, including 10,942 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 0.29 (6448 hom., cov: 31)
  • Exomes 𝑓: 0.30 (4494 hom.)
• Consequence: PAK1 NM_002576.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

Genes affected

PAK1 (HGNC:8590): (p21 (RAC1) activated kinase 1) This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Mutations in this gene have been associated with macrocephaly, seizures, and speech delay. Overexpression of this gene is also reported in many cancer types, and particularly in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]

PAK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK1	NM_002576.5	c.*611T>G		3_prime_UTR_variant	15/15	ENST00000356341.8	NP_002567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK1	ENST00000356341	c.*611T>G		3_prime_UTR_variant	15/15	1	NM_002576.5	ENSP00000348696.4
PAK1	ENST00000530617	c.*474T>G		3_prime_UTR_variant	15/15	2		ENSP00000433423.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43294 AN: 151768 Hom.: 6444 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.302 AC: 27296 AN: 90286 Hom.: 4494 Cov.: 0 AF XY: 0.306 AC XY: 13698 AN XY: 44782

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.285 AC: 43320 AN: 151886 Hom.: 6448 Cov.: 31 AF XY: 0.283 AC XY: 21013 AN XY: 74228

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.291

Alfa AF: 0.311 Hom.: 4584

Bravo AF: 0.277

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.79

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: rs2844337; hg19: chr11-77033708; COSMIC: COSV53698297; COSMIC: COSV53698297;