chr11-77332353-G-GGGGGGAGGGGAGGGGAGGGGAGGGGGGGAGGGTGGGGAAGGGGAGGGGAGGGGAGGGGGGAGGGGAGGGGGAAGGGGAGAGGGGAGGGGGGAGGGAGGGGGGAGGGGGAGGGGGAGGGGGAGGGGAGGGGGTAGGAGGAGGGGAAGGAAGGGAAGGATTGGAGGGGAAGCGAA

Variant names:

• chr11-77332353-G-GGGGGGAGGGGAGGGGAGGGGAGGGGGGGAGGGTGGGGAAGGGGAGGGGAGGGGAGGGGGGAGGGGAGGGGGAAGGGGAGAGGGGAGGGGGGAGGGAGGGGGGAGGGGGAGGGGGAGGGGGAGGGGAGGGGGTAGGAGGAGGGGAAGGAAGGGAAGGATTGGAGGGGAAGCGAA
• NM_002576.5:c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002576.5(PAK1):​c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PAK1 NM_002576.5 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.20
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002576.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK1	NM_002576.5	MANE Select	c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	NP_002567.3
	PAK1	NM_001128620.2		c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	NP_001122092.1	Q13153-2
	PAK1	NM_001376268.1		c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	NP_001363197.1	Q13153-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK1	ENST00000356341.8	TSL:1 MANE Select	c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	ENSP00000348696.4	Q13153-1
	PAK1	ENST00000278568.8	TSL:2	c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	ENSP00000278568.4	Q13153-2
	PAK1	ENST00000873292.1		c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron	N/A	ENSP00000543351.1

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Schizophrenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2

Splicing

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

Other links and lift over

hg19: chr11-77043398;