The missense variant in c.941A>G (p.Asn314Ser) in PAK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn314Ser variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Asn at position 314 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Asn314Ser in PAK1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_002576.5(PAK1):c.941A>G (p.Asn314Ser)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002576.5(PAK1):c.941A>G (p.Asn314Ser)
Variation ID: 2585489 Accession: VCV002585489.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.5 11: 77343876 (GRCh38) [ NCBI UCSC ] 11: 77054921 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 28, 2023 Oct 28, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_002576.5:c.941A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002567.3:p.Asn314Ser missense NM_001128620.2:c.941A>G NP_001122092.1:p.Asn314Ser missense NM_001376268.1:c.941A>G NP_001363197.1:p.Asn314Ser missense NM_001376269.1:c.941A>G NP_001363198.1:p.Asn314Ser missense NM_001376270.1:c.941A>G NP_001363199.1:p.Asn314Ser missense NM_001376271.1:c.941A>G NP_001363200.1:p.Asn314Ser missense NM_001376272.1:c.962A>G NP_001363201.1:p.Asn321Ser missense NM_001376273.1:c.941A>G NP_001363202.1:p.Asn314Ser missense NM_001376274.1:c.941A>G NP_001363203.1:p.Asn314Ser missense NM_001376275.1:c.941A>G NP_001363204.1:p.Asn314Ser missense NM_001376276.1:c.941A>G NP_001363205.1:p.Asn314Ser missense NM_001376277.1:c.941A>G NP_001363206.1:p.Asn314Ser missense NM_001376278.1:c.941A>G NP_001363207.1:p.Asn314Ser missense NM_001376279.1:c.941A>G NP_001363208.1:p.Asn314Ser missense NM_001376280.1:c.941A>G NP_001363209.1:p.Asn314Ser missense NM_001376281.1:c.941A>G NP_001363210.1:p.Asn314Ser missense NM_001376282.1:c.941A>G NP_001363211.1:p.Asn314Ser missense NM_001376283.1:c.941A>G NP_001363212.1:p.Asn314Ser missense NM_001376284.1:c.941A>G NP_001363213.1:p.Asn314Ser missense NM_001376285.1:c.941A>G NP_001363214.1:p.Asn314Ser missense NM_001376286.1:c.941A>G NP_001363215.1:p.Asn314Ser missense NM_001376287.1:c.941A>G NP_001363216.1:p.Asn314Ser missense NM_001376288.1:c.941A>G NP_001363217.1:p.Asn314Ser missense NM_001376289.1:c.941A>G NP_001363218.1:p.Asn314Ser missense NM_001376290.1:c.941A>G NP_001363219.1:p.Asn314Ser missense NM_001376291.1:c.941A>G NP_001363220.1:p.Asn314Ser missense NM_001376292.1:c.941A>G NP_001363221.1:p.Asn314Ser missense NM_001376293.1:c.941A>G NP_001363222.1:p.Asn314Ser missense NM_001376294.1:c.932A>G NP_001363223.1:p.Asn311Ser missense NM_001376295.1:c.822-3113A>G intron variant NM_001376301.1:c.692A>G NP_001363230.1:p.Asn231Ser missense NM_001376302.1:c.647A>G NP_001363231.1:p.Asn216Ser missense NM_001376303.1:c.653A>G NP_001363232.1:p.Asn218Ser missense NM_001376304.1:c.647A>G NP_001363233.1:p.Asn216Ser missense NM_001376305.1:c.647A>G NP_001363234.1:p.Asn216Ser missense NR_164797.1:n.1157A>G non-coding transcript variant NR_164798.1:n.1160A>G non-coding transcript variant NC_000011.10:g.77343876T>C NC_000011.9:g.77054921T>C NG_029900.2:g.135188A>G NG_029900.3:g.191133A>G - Protein change
- N231S, N321S, N216S, N218S, N314S, N311S
- Other names
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- Canonical SPDI
- NC_000011.10:77343875:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| PAK1 | - | - |
GRCh38 GRCh37 |
95 | 104 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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- | RCV003338105.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047027.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The missense variant in c.941A>G (p.Asn314Ser) in PAK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our … (more)
The missense variant in c.941A>G (p.Asn314Ser) in PAK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn314Ser variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Asn at position 314 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Asn314Ser in PAK1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. (less)
Clinical Features:
Global developmental delay (present) , Poor speech (present) , Postnatal macrocephaly (present) , Seizure (present)
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The missense variant in c.941A>G (p.Asn314Ser) in PAK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn314Ser variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Asn at position 314 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Asn314Ser in PAK1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.