VCV000372467.41 - ClinVar

NM_181523.3(PIK3R1):c.1425+1G>A

Germline

Classification

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.

(14)

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.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_181523.3(PIK3R1):c.1425+1G>A

Variation ID: 372467 Accession: VCV000372467.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q13.1 5: 68293835 (GRCh38) [ NCBI UCSC ] 5: 67589663 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Jan 9, 2017	Nov 17, 2024	Nov 1, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_181523.3:c.1425+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001242466.2:c.336+1G>A		splice donor
NM_181504.4:c.615+1G>A		splice donor
NM_181524.2:c.525+1G>A		splice donor
NC_000005.10:g.68293835G>A
NC_000005.9:g.67589663G>A
NG_012849.2:g.83080G>A
LRG_453:g.83080G>A
LRG_453t1:c.1425+1G>A

... more HGVS ... less HGVS

Protein change

Other names

NM_181523.3:c.1425+1G>A
IVS11DS, G-A, +1

Canonical SPDI

NC_000005.10:68293834:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

sequence_variant_affecting_splicing; Sequence Ontology [ SO:1000071]

Intron inclusion between exons 11 & 12, based on review of RNA-seq in TCGA-D7-8572-01A tumor which has PIK3R1 NM_181523.3:c.1425+1G>A variant [submitted by MutSpliceDB: a database of splice sites variants effects on splicing, NIH]

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA16042620 OMIM: 171833.0009 dbSNP: rs587777709 VarSome

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
Gene	OMIM	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.
PIK3R1		-	-	GRCh38 GRCh37	546	562

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.
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Nov 1, 2023	RCV000413301.25
Immunodeficiency 36	Pathogenic (1)	no assertion criteria provided	Mar 15, 2023	RCV000515768.3
Inborn genetic diseases	Pathogenic (1)	criteria provided, single submitter	Dec 15, 2017	RCV001266930.3
SHORT syndrome	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jul 27, 2022	RCV000987525.4
Agammaglobulinemia 7, autosomal recessive Immunodeficiency 36 SHORT syndrome	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 5, 2023	RCV000705809.10
Inherited Immunodeficiency Diseases	Pathogenic (1)	criteria provided, single submitter	Jan 1, 2019	RCV001027613.2
See cases	Pathogenic (1)	criteria provided, single submitter	Dec 21, 2022	RCV003156092.2
PIK3R1-related disorder	Pathogenic (1)	no assertion criteria provided	Jan 11, 2024	RCV003922673.3

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.
Pathogenic (Dec 07, 2016)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000490721.1 First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017	Comment: The c.1425+1G>A pathogenic variant has been reported previously in association with PASLI disease (Lucas et al., 2014). cDNA studies indicated that c.1425+1G>A results in the … (more) The c.1425+1G>A pathogenic variant has been reported previously in association with PASLI disease (Lucas et al., 2014). cDNA studies indicated that c.1425+1G>A results in the skipping of exon 11 (Lucas et al., 2014). This splice site variant destroys the canonical splice donor site in intron 11. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1425+1G>A variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret this variant to be pathogenic. (less)
Pathogenic (Oct 19, 2018)	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme) Method: clinical testing	Not provided Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV000928008.1 First in ClinVar: Jul 25, 2019 Last updated: Jul 25, 2019 Comment: Patient analyzed with Primary Immunodeficiency Panel
Likely pathogenic (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	SHORT syndrome Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136838.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Pathogenic (Jan 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Inherited Immunodeficiency Diseases Affected status: yes Allele origin: germline	NIHR Bioresource Rare Diseases, University of Cambridge Accession: SCV001190185.1 First in ClinVar: Mar 26, 2020 Last updated: Mar 26, 2020	Clinical Features: Abnormality of the respiratory system (present) , B lymphocytopenia (present) , Elevated proportion of CD4-negative, CD8-negative, alpha-beta regulatory T cells (present) , IgA deficiency (present) … (more) Abnormality of the respiratory system (present) , B lymphocytopenia (present) , Elevated proportion of CD4-negative, CD8-negative, alpha-beta regulatory T cells (present) , IgA deficiency (present) , Recurrent infections (present) (less)
Pathogenic (Feb 21, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	SHORT syndrome Affected status: yes Allele origin: unknown	Baylor Genetics Accession: SCV001520009.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021	Comment: This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Pathogenic (Mar 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	SHORT syndrome Agammaglobulinemia 7, autosomal recessive Immunodeficiency 36 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002813280.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Dec 15, 2017)	criteria provided, single submitter (Ambry exome assertion method (8-5-2015)) Method: clinical testing	Inborn genetic diseases Affected status: yes Allele origin: germline	Ambry Genetics Accession: SCV001445111.2 First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023	Publications: PubMed (3) PubMed: 27076228‚ 25133428‚ 27116393 Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian/N European/Irish/Hispanic/Nicaraguan
Pathogenic (Dec 21, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	See cases Affected status: yes Allele origin: de novo	Center for Personalized Medicine, Children's Hospital Los Angeles Accession: SCV003845300.1 First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023	Clinical Features: Abnormal T cell morphology (present) , Bifid nose (present) , Delayed skeletal maturation (present) , Depressed nasal bridge (present) , Dolichocephaly (present) , Failure to … (more) Abnormal T cell morphology (present) , Bifid nose (present) , Delayed skeletal maturation (present) , Depressed nasal bridge (present) , Dolichocephaly (present) , Failure to thrive (present) , Immunodeficiency (present) , Fetal growth restriction (present) , Microcephaly (present) , Midface retrusion (present) , Neonatal hypoglycemia (present) , Precocious puberty (present) , Renal tubular acidosis (present) , Short stature (present) (less)
Pathogenic (Oct 05, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	SHORT syndrome Immunodeficiency 36 Agammaglobulinemia 7, autosomal recessive Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000834824.7 First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024	Publications: PubMed (7) PubMed: 28492532‚ 25488983‚ 25939554‚ 27076228‚ 27116393‚ 27693481‚ 28302518 Comment: This sequence change affects a donor splice site in intron 11 of the PIK3R1 gene. RNA analysis indicates that disruption of this splice site induces … (more) This sequence change affects a donor splice site in intron 11 of the PIK3R1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with hypogammaglobulinemia with elevated IgM, activated PI3K-delta syndrome, and SHORT syndrome (PMID: 25488983, 25939554, 27076228, 27116393, 27693481, 28302518). In at least one individual the variant was observed to be de novo. This variant is also known as g.67589663G>A. ClinVar contains an entry for this variant (Variation ID: 372467). Studies have shown that disruption of this splice site results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 27076228). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Nov 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001961884.20 First in ClinVar: Oct 08, 2021 Last updated: Oct 20, 2024	Comment: PIK3R1: PM6:Strong, PM2, PS4:Moderate, PP3, PS3:Supporting Number of individuals with the variant: 3
Pathogenic (Jul 27, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	SHORT syndrome (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center Accession: SCV005397363.1 First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024	Publications: PubMed (6) PubMed: 25488983‚ 27076228‚ 28302518‚ 27116393‚ 27693481‚ 25939554 Comment: This sequence variant is a single nucleotide substitution (G>A) at the +1 position downstream of the exon 11 canonical splice donor site of the PIK3R1 … (more) This sequence variant is a single nucleotide substitution (G>A) at the +1 position downstream of the exon 11 canonical splice donor site of the PIK3R1 gene. This is a previously reported variant (ClinVar) which has been observed as a de novo variant in multiple individuals with a combition of phenotypes including short stature, immunodeficiency, hyper IgM syndrome, and hyperactivation of PI3K and AKT (PMID: 28302518, 27076228, 27693481, 25939554, 25488983, 27116393). This variant is not present in approximately 210300 alleles in the gnomAD control population dataset. Splicing studies show that this variant leads to an in-frame deletion of exon 11 (PMID: 25488983, 27076228); the variant protein is constitutively active, due to its ibility to properly interact with p110delta (PMID: 25488983). Based on the available evidence, we consider this variant to be pathogenic. ACMG Criteria: PM1, PM2, PM4, PP3, PP4, PS2, PS3, PS4 (less)
Pathogenic (Mar 15, 2023)	no assertion criteria provided Method: literature only	IMMUNODEFICIENCY 36 WITH LYMPHOPROLIFERATION Affected status: not provided Allele origin: germline	OMIM Accession: SCV000611865.2 First in ClinVar: Dec 08, 2017 Last updated: Mar 18, 2023	Publications: PubMed (3) PubMed: 25488983‚ 25939554‚ 27076228 Comment on evidence: In a 5-year-old Chinese boy with immunodeficiency-36 with lymphoproliferation (IMD36; 616005), who also exhibited lymphadenopathy, hepatomegaly, and severe juvenile rheumatoid arthritis, Lucas et al. (2014) … (more) In a 5-year-old Chinese boy with immunodeficiency-36 with lymphoproliferation (IMD36; 616005), who also exhibited lymphadenopathy, hepatomegaly, and severe juvenile rheumatoid arthritis, Lucas et al. (2014) identified heterozygosity for a c.1425+1G-A mutation (c.1425+1G-A, NM_181523.2) in intron 11 of the PIK3R1 gene. In a 9-month-old Albanian girl, a 3-year-old Italian boy, and a 3.5-year-old Swedish girl with recurrent respiratory infections and poor growth, who had hypogammaglobulinemia with elevated serum IgM levels and lymphoproliferation, Lougaris et al. (2015) identified heterozygosity for the c.1425+1G-A mutation in the PIK3R1 gene. The mutation was shown to have occurred de novo in 2 of the patients; the genotype of the Swedish parents was unknown. In 4 unrelated children (patients 1-4) with immunodeficiency and elevated IgM levels, lymphadenopathy, and short stature, Petrovski et al. (2016) identified heterozygosity for the c.1425+1G-A mutation in PIK3R1. The mutation was confirmed to have arisen de novo in 3 of the patients; it was not found in the fourth child's unaffected mother, but DNA was unavailable from the father. Analysis of PCR products from patient 1 and his parents demonstrated that the mutation causes skipping of exon 11, with direct exon 10 to exon 12 splicing. Results of functional analysis using patient cells were consistent with constitutive activation of the PI3K-mTOR (601231) signaling. Patient 4, a 5-year-old Caucasian girl, also exhibited features of SHORT syndrome (269880); the authors noted that no results of immune studies had been reported for SHORT syndrome patients. (less)
Pathogenic (Jan 11, 2024)	no assertion criteria provided Method: clinical testing	PIK3R1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004744308.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: The PIK3R1 c.1425+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported as a recurrent … (more) The PIK3R1 c.1425+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported as a recurrent de novo mutation in multiple individuals with activated phosphoinositide 3-kinase δ syndrome type 2 (APDS2) (Lucas et al. 2014. PubMed ID: 25488983; Lougaris et al. 2015. PubMed ID: 25939554; Petrovski et al. 2016. PubMed ID: 27076228; Olbrich et al. 2016. PubMed ID: 27116393; Elkaim et al. 2016. PubMed ID: 27221134; Yazdani et al. 2019. PubMed ID: 30799802). RNA analysis has shown that this variant leads to an in-frame deletion of 42 amino acid residues, and in vitro functional studies using tranformed patient B cells have shown that this deletion leads to reduced p85α protein expression, constitutive activation of the PI3K complex, and upregulation of downstream AKT and mTOR signaling pathways (Petrovski et al. 2016. PubMed ID: 27076228). This variant has not been reported in a large population database, indicating this variant is rare. Several additional variants that disrupt the same splice donor site (c.1425+1G>C/T, +2T>A/G, +2_+3delTG, etc.) have been reported in multiple individuals with ADPS-related phenotypes (Deau et al. 2014. PubMed ID: 25133428; Elkaim et al. 2016. PubMed ID: 27221134). Variants that disrupt the consensus splice donor site in PIK3R1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
not provided (-)	no classification provided Method: research	not provided Affected status: not applicable Allele origin: somatic	MutSpliceDB: a database of splice sites variants effects on splicing, NIH Accession: SCV002106363.2 First in ClinVar: Mar 19, 2022 Last updated: Mar 28, 2022	Other databases https://brb.nci.nih.gov/cgi-bin/… https://brb.nci.nih.gov/cgi-bin/splicing/splicing_evidence.cgi?caid=CA16042620 Comment on evidence: Intron inclusion between exons 11 & 12, based on review of RNA-seq in TCGA-D7-8572-01A tumor which has PIK3R1 NM_181523.3:c.1425+1G>A variant Method: Based on review of RNA-seq data in sample with variant. Result: Intron inclusion between exons 11 & 12
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Comment:

The c.1425+1G>A pathogenic variant has been reported previously in association with PASLI disease (Lucas et al., 2014). cDNA studies indicated that c.1425+1G>A results in the skipping of exon 11 (Lucas et al., 2014). This splice site variant destroys the canonical splice donor site in intron 11. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1425+1G>A variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret this variant to be pathogenic.

Comment:

This sequence change affects a donor splice site in intron 11 of the PIK3R1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with hypogammaglobulinemia with elevated IgM, activated PI3K-delta syndrome, and SHORT syndrome (PMID: 25488983, 25939554, 27076228, 27116393, 27693481, 28302518). In at least one individual the variant was observed to be de novo. This variant is also known as g.67589663G>A. ClinVar contains an entry for this variant (Variation ID: 372467). Studies have shown that disruption of this splice site results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 27076228). For these reasons, this variant has been classified as Pathogenic.

Comment:

This sequence variant is a single nucleotide substitution (G>A) at the +1 position downstream of the exon 11 canonical splice donor site of the PIK3R1 gene. This is a previously reported variant (ClinVar) which has been observed as a de novo variant in multiple individuals with a combition of phenotypes including short stature, immunodeficiency, hyper IgM syndrome, and hyperactivation of PI3K and AKT (PMID: 28302518, 27076228, 27693481, 25939554, 25488983, 27116393). This variant is not present in approximately 210300 alleles in the gnomAD control population dataset. Splicing studies show that this variant leads to an in-frame deletion of exon 11 (PMID: 25488983, 27076228); the variant protein is constitutively active, due to its ibility to properly interact with p110delta (PMID: 25488983). Based on the available evidence, we consider this variant to be pathogenic. ACMG Criteria: PM1, PM2, PM4, PP3, PP4, PS2, PS3, PS4

Comment:

The PIK3R1 c.1425+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported as a recurrent de novo mutation in multiple individuals with activated phosphoinositide 3-kinase δ syndrome type 2 (APDS2) (Lucas et al. 2014. PubMed ID: 25488983; Lougaris et al. 2015. PubMed ID: 25939554; Petrovski et al. 2016. PubMed ID: 27076228; Olbrich et al. 2016. PubMed ID: 27116393; Elkaim et al. 2016. PubMed ID: 27221134; Yazdani et al. 2019. PubMed ID: 30799802). RNA analysis has shown that this variant leads to an in-frame deletion of 42 amino acid residues, and in vitro functional studies using tranformed patient B cells have shown that this deletion leads to reduced p85α protein expression, constitutive activation of the PI3K complex, and upregulation of downstream AKT and mTOR signaling pathways (Petrovski et al. 2016. PubMed ID: 27076228). This variant has not been reported in a large population database, indicating this variant is rare. Several additional variants that disrupt the same splice donor site (c.1425+1G>C/T, +2T>A/G, +2_+3delTG, etc.) have been reported in multiple individuals with ADPS-related phenotypes (Deau et al. 2014. PubMed ID: 25133428; Elkaim et al. 2016. PubMed ID: 27221134). Variants that disrupt the consensus splice donor site in PIK3R1 are expected to be pathogenic. This variant is interpreted as pathogenic.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
sequence_variant_affecting_splicing (SO:1000071)	Based on review of RNA-seq data in sample with variant.	Intron inclusion between exons 11 & 12	MutSpliceDB: a database of splice sites variants effects on splicing, NIH Accession: SCV002106363.2	Other databases https://brb.nci.nih.gov/cgi-bin/… Comment: Intron inclusion between exons 11 & 12, based on review of RNA-seq in TCGA-D7-8572-01A tumor which has PIK3R1 NM_181523.3:c.1425+1G>A variant

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two.	Bravo García-Morato M	Clinical immunology (Orlando, Fla.)	2017	PMID: 28302518
Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype of respiratory infections.	Martínez-Saavedra MT	Clinical immunology (Orlando, Fla.)	2016	PMID: 27693481
Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature.	Olbrich P	Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology	2016	PMID: 27116393
Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.	Petrovski S	Journal of clinical immunology	2016	PMID: 27076228
Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype.	Lougaris V	Clinical immunology (Orlando, Fla.)	2015	PMID: 25939554
Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K.	Lucas CL	The Journal of experimental medicine	2014	PMID: 25488983
A human immunodeficiency caused by mutations in the PIK3R1 gene.	Deau MC	The Journal of clinical investigation	2014	PMID: 25133428
https://brb.nci.nih.gov/cgi-bin/splicing/splicing_evidence.cgi?caid=CA16042620	-	-	-	-

Text-mined citations for rs587777709 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_181523.3(PIK3R1):c.1425+1G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs587777709 ...