11-77332353-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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK1	NM_002576.5	c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron_variant	Intron 14 of 14	ENST00000356341.8	NP_002567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK1	ENST00000356341.8	c.1551+376_1551+377insTTCGCTTCCCCTCCAATCCTTCCCTTCCTTCCCCTCCTCCTACCCCCTCCCCTCCCCCTCCCCCTCCCCCTCCCCCCTCCCTCCCCCCTCCCCTCTCCCCTTCCCCCTCCCCTCCCCCCTCCCCTCCCCTCCCCTTCCCCACCCTCCCCCCCTCCCCTCCCCTCCCCTCCCCC		intron_variant	Intron 14 of 14	1	NM_002576.5	ENSP00000348696.4

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Schizophrenia Uncertain:1

Nov 11, 2022

Department of Psychiatry, The University of Hong Kong

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

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;