rs3019238

Variant names:

• chr11-77493821-G-A
• rs3019238
• XM_024448560.2:c.-301-19152C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-77493821-G-A
• chr11-77493821-G-C
• chr11-77493821-G-T

Variant summary

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

The XM_024448560.2(PAK1):​c.-301-19152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,980 control chromosomes in the GnomAD database, including 28,605 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 0.59 (28605 hom., cov: 31)
• Consequence: PAK1 XM_024448560.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with macrocephaly, seizures, and speech delay

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK1	XM_024448560.2	c.-301-19152C>T		intron_variant	Intron 2 of 16		XP_024304328.1
PAK1	XM_047427049.1	c.-581C>T		upstream_gene_variant			XP_047283005.1
PAK1	XM_047427054.1	c.-581C>T		upstream_gene_variant			XP_047283010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89490 AN: 151862 Hom.: 28569 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.589 AC: 89585 AN: 151980 Hom.: 28605 Cov.: 31 AF XY: 0.594 AC XY: 44114 AN XY: 74258

African (AFR) AF: 0.830 AC: 34438 AN: 41476

American (AMR) AF: 0.642 AC: 9800 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3600 AN: 5168

South Asian (SAS) AF: 0.557 AC: 2685 AN: 4818

European-Finnish (FIN) AF: 0.504 AC: 5301 AN: 10526

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30015 AN: 67946

Other (OTH) AF: 0.560 AC: 1180 AN: 2106

Alfa AF: 0.491 Hom.: 83593

Bravo AF: 0.612

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		0.031

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3019238; hg19: chr11-77204866;