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Variant interpretation report

PIK3CA c.2850A>G, p.(Glu950=)

NM_006218.4:c.2850A>G NP_006209.2:p.(Glu950=) View identifiers
Classification
Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About PIK3CA

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is ClinGen PIK3CA VCEP v1.1. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 2 Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM1Supporting
PM1 · supporting

Residue 950 (Glu950) falls within the C-terminal kinase domain (AA 797-1068) defined in Table 4 of the ClinGen Brain Malformations VCEP specification (v1.1) as a critical functional domain for PIK3CA. Under this VCEP, PM1 is awarded at Supporting strength for residues located within approved Table 4 domains, independent of hotspot recurrence.

PM2Supporting
PM2 · supporting

This variant is extremely rare in population databases. In gnomAD v2.1, it is present at AF=0.00080% (2/248,508 alleles) and in gnomAD v4.1 at AF=0.00006% (1/1,611,758 alleles), with zero homozygotes in both datasets. The highest subpopulation frequency is 0.00177% in European (non-Finnish) in v2.1. Under the VCEP, PM2 is awarded at Supporting strength for variants absent or rare (≤1 person) in ethnically-matched controls. The pooled allele count across datasets supports PM2 at supporting level.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

ClinGen Brain Malformations Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1 v1.1 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM1 supporting, PM2 supporting; combination = 2 supporting, which maps to VUS.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1
gnomAD v2.1
Population frequency
1 / 1,611,758 alleles

gnomAD v4.1: 1 / 1,611,758 alleles. Recorded AF 6.20441e-07. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.04803e-06; MAF= 0.00080%, 2/248508 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.7734e-05; MAF= 0.00177%, 2/112778 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI score
0.050 maximum delta

Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.

No listed criterion applied SpliceAI ↗
ClinVar submissions
1 reported laboratory submissions

1 Likely benign. ClinVar API review status: criteria provided, single submitter.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

For specialists

Technical detail

ACMG/AMP criteria under ClinGen PIK3CA VCEP v1.1, with the data and sources behind each one.

26 criteria with recorded statuses: 2 met · 9 not met · 2 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Met Not met Not assessed Not applicable

NM_006218.4:c.2850A>G (p.Glu950=) is a synonymous variant in PIK3CA exon 20. The ClinGen Brain Malformations VCEP (v1.1) framework was applied for criterion adjudication.

The variant falls within the C-terminal kinase domain (AA 797-1068), a Table 4 critical functional domain for PIK3CA per the VCEP specification, meeting PM1 at Supporting strength.

The variant is extremely rare in population databases: gnomAD v2.1 AF=0.00080% (2/248,508 alleles), gnomAD v4.1 AF=0.00006% (1/1,611,758 alleles), with zero homozygotes. PM2 is met at Supporting strength under VCEP rules.

PVS1, PS1, PM5, PM6, PP1, PP2, PP3, PP4, PP5, BS4, BP1, BP6, and BP3 are not applicable under the VCEP framework or due to the synonymous nature of the variant.

SpliceAI predicts no significant splicing impact (max delta=0.05), but BP4 requires two of three tools (varSEAK, SpliceAI, MaxEntScan) per VCEP specifications; only SpliceAI is available. BP7 requires a PhyloP score <0.1, which is not available. Both BP4 and BP7 remain not assessed.

No functional studies, de novo reports, case observations, or segregation data were identified for this synonymous variant. PS2, PS3, PS4, BS2, BS3, BP2, and BP5 are not met.

With PM1_Supporting (+1) and PM2_Supporting (+1), the total points sum to +2. Per the VCEP Tavtigian point-combination framework (Pathogenic ≥10, Likely Pathogenic 6-9, VUS 0-5, Likely Benign -6 to -1, Benign <-6), a score of +2 falls within the VUS (0-5) range.

Met · 2

PM1 SupportingResidue 950 (Glu950) falls within the C-terminal kinase domain (AA 797-1068) defined in Table 4 of the ClinGen Brain Malformations VCEP specification (v1.1) as a critical functional domain for PIK3CA. Under this VCEP, PM1 is awarded at Supporting strength for residues located within approved Table 4 domains, independent of hotspot recurrence. Details ▾Hide ▴
Evidence considered
  • VCEP Table 4 approved PIK3CA kinase domain: AA 797-1068. Residue E950 is within this interval. Domain membership established.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PM2 SupportingThis variant is extremely rare in population databases. In gnomAD v2.1, it is present at AF=0.00080% (2/248,508 alleles) and in gnomAD v4.1 at AF=0.00006% (1/1,611,758 alleles), with zero homozygotes in both datasets. The highest subpopulation frequency is 0.00177% in European (non-Finnish) in v2.1. Under the VCEP, PM2 is awarded at Supporting strength for variants absent or rare (≤1 person) in ethnically-matched controls. The pooled allele count across datasets supports PM2 at supporting level. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: 2/248
  • 508 (AF 8.05e-06)
  • 0 hom. gnomAD v4.1: 1/1
  • 611
  • 758 (AF 6.20e-07)
  • 0 hom. grpmax FAF v2.1: 2.95e-06.
Sources

Not met · 9 · evaluated, threshold not reached

PS2 VCEP PS2 requires de novo evidence with confirmed maternity/paternity plus tissue differential allele fraction (strong) or at minimum criterion 1 alone (moderate). No de novo data are available for this variant in the case materials or literature. The ClinVar submission from Ambry Genetics (SCV002749861) is germline origin but provides no de novo confirmation. Details ▾Hide ▴
Evidence considered
  • No de novo reports identified for this variant.
Still missing
  • Parental testing data not available for this case.
Sources
PS3 No functional studies were identified for NM_006218.4:c.2850A>G, a synonymous variant. OncoKB lists this variant as 'Unknown Oncogenic Effect' with no curated PMIDs. The reviewed publications (PMID:23619275, PMID:25730230) are policy statements about carrier screening that do not address PIK3CA functional data. No variant-specific or systematic-range functional characterization is available. Details ▾Hide ▴
Evidence considered
  • OncoKB: Unknown Oncogenic Effect
  • no curated PMIDs. COSMIC: not found. No functional assay data for this variant in literature.
Still missing
  • No functional studies exist for this synonymous variant.
Sources
PS4 VCEP PS4 requires phenotype point assignment (Tables 2A/2B) and is dependent on PM2 being met first for absent/rare in controls. No case reports of this variant in individuals with brain malformations were identified in the literature or ClinVar submissions. The variant has not been reported in COSMIC. Without affected case data, no PS4 points can be assigned. Details ▾Hide ▴
Evidence considered
  • No affected cases in ClinVar (1 submission: Likely benign
  • no phenotype data). COSMIC: absent. No case reports in reviewed literature.
Still missing
  • No affected individuals reported with this variant.
Sources
BA1 VCEP BA1 threshold is allele frequency >0.0926%. The maximum observed population frequency for this variant is 0.00177% (European non-Finnish, gnomAD v2.1), which is approximately 50-fold below the BA1 threshold. This variant does not meet the stand-alone benign allele frequency criterion. Details ▾Hide ▴
Evidence considered
  • Max AF: 0.00177% (gnomAD v2.1 NFE). VCEP BA1 threshold: >0.0926%. Not met.
Sources
BS1 VCEP BS1 threshold is allele frequency >0.0185%. The maximum observed population frequency for this variant is 0.00177% (European non-Finnish, gnomAD v2.1), which is approximately 10-fold below the BS1 threshold. This variant does not meet the strong benign allele frequency criterion. Details ▾Hide ▴
Evidence considered
  • Max AF: 0.00177% (gnomAD v2.1 NFE). VCEP BS1 threshold: >0.0185%. Not met.
Sources
BS2 VCEP BS2 requires ≥3 homozygotes in gnomAD or ≥3 heterozygous in well-phenotyped family members. This variant has zero homozygotes in both gnomAD v2.1 and v4.1. No well-phenotyped family member data are available in the case materials. Details ▾Hide ▴
Evidence considered
  • gnomAD: 0 homozygotes in v2.1 (248
  • 508 exomes) and v4.1 (1
  • 611
  • 758 alleles). No homozygous or phenotyped family member data.
Sources
BS3 No well-established in vitro or in vivo functional studies demonstrating no damaging effect on protein function or splicing exist for this variant. OncoKB lists this variant as 'Unknown Oncogenic Effect' with no curated PMIDs. The reviewed publications (PMID:23619275, PMID:25730230) are policy statements unrelated to PIK3CA functional biology. Details ▾Hide ▴
Evidence considered
  • No functional studies identified that demonstrate benign effect for this synonymous variant.
Still missing
  • No functional studies evaluating this variant.
Sources
BP2 BP2 requires observation of this variant in cis or trans with a known pathogenic variant in the same gene. No such co-occurrence data are available in the case materials, ClinVar submissions, or reviewed literature. Details ▾Hide ▴
Evidence considered
  • No evidence of co-occurrence with a known pathogenic PIK3CA variant.
Still missing
  • Phasing data or co-occurrence with pathogenic variant not available.
Sources
BP5 BP5 requires evidence that the variant is found in a case with an alternate molecular basis for disease. No such evidence is available for this variant in the case materials or literature. Details ▾Hide ▴
Evidence considered
  • No evidence of an alternate molecular diagnosis in individuals carrying this variant.
Sources

Not assessed · 2 · no assessment recorded

BP4 VCEP BP4 requires two out of three splicing prediction tools (varSEAK, SpliceAI, MaxEntScan) to predict no impact on splicing. Only SpliceAI data is available (max delta = 0.05, indicating no significant splice impact). Without varSEAK and MaxEntScan scores, the criterion cannot be fully assessed. SpliceAI alone suggests no splicing effect, but this is insufficient to meet the VCEP's 2-of-3 tool requirement. Details ▾Hide ▴
Evidence considered
  • SpliceAI delta = 0.05 (no significant impact). 1 of 3 required tools available. varSEAK and MaxEntScan data missing.
Still missing
  • varSEAK and MaxEntScan splicing predictions not available.
Sources
BP7 VCEP BP7 is applicable to synonymous variants and requires a PhyloP score <0.1 indicating the nucleotide is non-conserved. This is a synonymous variant (p.Glu950=) but the PhyloP conservation score is not available in the prefetch, evidence_brief, or any other case output. Without the PhyloP score, BP7 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • Synonymous variant eligible for BP7 assessment. PhyloP score not available.
Still missing
  • PhyloP conservation score not available for nucleotide c.2850.
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PVS1 is not applicable because the disease mechanism for PIK3CA-related brain malformations is gain of function, not loss of function or haploinsufficiency. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PVS1 not applicable for PIK3CA.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PS1 N/APS1 requires the same amino acid change as a previously established pathogenic variant. This variant (NM_006218.4:c.2850A>G) is synonymous (p.Glu950=) and does not alter the amino acid; there is no amino acid change to compare. Details ▾Hide ▴
Evidence considered
  • Variant is synonymous p.(Glu950=)
  • no amino acid alteration occurs.
Sources
PM5 N/APM5 is defined as a novel missense change at an amino acid residue where a different pathogenic missense change has been reported. This variant is synonymous (p.Glu950=), not missense. The pm5_candidates assessment confirms the variant class is not missense-like and is ineligible for classic PM5. Details ▾Hide ▴
Evidence considered
  • Synonymous variant p.(Glu950=)
  • not a missense change. PM5 candidate search yielded no eligible comparators.
Sources
pm5_candidatescspec ↗
PM6 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PM6 is not applicable because this point is addressed according to PS2 and will not be used. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PM6 not applicable
  • addressed via PS2.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP1 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PP1 is not applicable since disease-causing variants are germline mosaic, de novo, or mosaic. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PP1 not applicable.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP2 N/APP2 is defined in the original ACMG/AMP framework as a missense variant in a gene with a low rate of benign missense variation. This variant is synonymous (p.Glu950=), not missense. The VCEP rule uses missense constraint z-score, which is applicable to missense variant evaluation, not synonymous changes. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • PP2 is specific to missense variants per original ACMG definition.
Sources
PP3 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PP3 is not applicable since these variants are gain-of-function and traditional mutation pathogenicity prediction algorithms focus on loss-of-function mechanisms. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PP3 not applicable for PIK3CA (GOF mechanism).
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP4 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PP4 is not applicable since this criterion is accounted for under PS4. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PP4 not applicable
  • phenotype specificity addressed under PS4.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP5 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PP5 not for use.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BS4 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that BS4 is not applicable as these are de novo, germline mosaic, or post-zygotic mutations. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares BS4 not applicable.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP1 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that BP1 is not applicable because loss of function is not the disease mechanism for PIK3CA. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares BP1 not applicable
  • GOF mechanism.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP6 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares BP6 not for use.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PS5 N/APS5 is not a standard ACMG/AMP criterion. The ACMG 2015 guidelines define criteria PVS1, PS1-PS4, PM1-PM6, PP1-PP5. No PS5 criterion exists in the framework. Details ▾Hide ▴
Evidence considered
  • PS5 does not exist in the ACMG/AMP 2015 framework.

Identifiers

Gene
PIK3CA
Transcript
NM_006218.4
Coding (HGVS c.)
NM_006218.4:c.2850A>G
Protein (HGVS p.)
NP_006209.2:p.(Glu950=)
GRCh38
chr3:179230290 A>G
GRCh37
chr3:178948078 A>G
ClinVar
1796825

Gene diagram

Every interpreted variant in PIK3CA, mapped onto the exon structure of NM_006218.4. Select a row to find it on the plot.

PIK3CANM_006218.4
Fetching transcript structure from UCSC…
gnomAD v4.1 1 / 1,611,758 alleles AF 6.2e-07 · 0 homozygotes
gnomAD v2.1 2 / 248,508 alleles AF 8.05e-06 · 0 homozygotes · FAF 2.95e-06
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,611,758 alleles · 0 hom
European (non-Finnish)1 / 1,178,374 8.5e-07
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 8e-06 · 2 / 248,508 alleles · 0 hom · FAF 3e-06
European (non-Finnish)2 / 112,778 1.8e-05
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.20441e-07; MAF= 0.00006%, 1/1611758 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.48627e-07; MAF= 0.00008%, 1/1178374 alleles, homozygotes = 0).

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.04803e-06; MAF= 0.00080%, 2/248508 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.7734e-05; MAF= 0.00177%, 2/112778 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +25 bp
0.040
SpliceAI acceptor gainat +1 bp
0.000
SpliceAI donor lossat +86 bp
0.050
SpliceAI donor gainat -187 bp
0.000
Pangolin splice lossmagnitude shown
-0.020
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 VCEP BP4 requires two out of three splicing prediction tools (varSEAK, SpliceAI, MaxEntScan) to predict no impact on splicing. Only SpliceAI data is available (max delta = 0.05, indicating no significant splice impact). Without varSEAK and MaxEntScan scores, the criterion cannot be fully assessed. SpliceAI alone suggests no splicing effect, but this is insufficient to meet the VCEP's 2-of-3 tool requirement. Details ▾Hide ▴
Evidence considered
  • SpliceAI delta = 0.05 (no significant impact). 1 of 3 required tools available. varSEAK and MaxEntScan data missing.
Still missing
  • varSEAK and MaxEntScan splicing predictions not available.
Sources
BP7 VCEP BP7 is applicable to synonymous variants and requires a PhyloP score <0.1 indicating the nucleotide is non-conserved. This is a synonymous variant (p.Glu950=) but the PhyloP conservation score is not available in the prefetch, evidence_brief, or any other case output. Without the PhyloP score, BP7 cannot be assessed. Details ▾Hide ▴
Evidence considered
  • Synonymous variant eligible for BP7 assessment. PhyloP score not available.
Still missing
  • PhyloP conservation score not available for nucleotide c.2850.
Sources
PP3 VCEPThe ClinGen Brain Malformations VCEP (v1.1) states that PP3 is not applicable since these variants are gain-of-function and traditional mutation pathogenicity prediction algorithms focus on loss-of-function mechanisms. Details ▾Hide ▴
Evidence considered
  • VCEP specification explicitly declares PP3 not applicable for PIK3CA (GOF mechanism).
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).

5 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

  • ACMG position statement on prenatal/preconception expanded carrier screening.
    ACMG position statement on prenatal/preconception expanded carrier screening. Discusses criteria for selecting disorders for population-based carrier screening panels. PIK3CA and NM_006218.4:c.2850A>G were not mentioned.
    Does not name this variant
    PMID 23619275 ↗
  • Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.
    Edwards JG et al. · 2015
    Joint statement on expanded carrier screening in reproductive medicine from ACMG, ACOG, NSGC, Perinatal Quality Foundation, and SMFM. Provides points to consider for expanded carrier screening panels. PIK3CA and NM_006218.4:c.2850A>G were not mentioned.
    Does not name this variant
    PMID 25730230 ↗
  • Including the initial newborn screening bloodspot collection device serial number on birth certificates: basis and recommendations from the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.
    Therrell BL et al. · 2013
    Recommendations on including newborn screening bloodspot serial numbers on birth certificates from the HHS Advisory Committee on Heritable Disorders in Newborns and Children. PIK3CA and NM_006218.4:c.2850A>G were not mentioned.
    Does not name this variant
    PMID 23037933 ↗
  • Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].
    Skirton H et al. · 2014
    European guidelines for offering prenatal diagnostic tests in clinical practice. PIK3CA and NM_006218.4:c.2850A>G were not mentioned.
    Does not name this variant
    PMID 24022298 ↗
  • Parental permission for pilot newborn screening research: guidelines from the NBSTRN.
    Botkin JR et al. · 2014
    Guidelines for parental permission for pilot newborn screening research from the NBSTRN. PIK3CA and NM_006218.4:c.2850A>G were not mentioned.
    Does not name this variant
    PMID 24394680 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.20441e-07; MAF= 0.00006%, 1/1611758 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.48627e-07; MAF= 0.00008%, 1/1178374 alleles, homozygotes = 0).

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.04803e-06; MAF= 0.00080%, 2/248508 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.7734e-05; MAF= 0.00177%, 2/112778 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 1796825)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.