About ANKRD26
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
ANKRD26 c.-140C>G, p.?
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
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 Not recorded. 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: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BA1Stand alone
BA1 · stand alone
This variant is far above the benign stand-alone population threshold. The allele frequency is 0.0640054 (6.40054%) in gnomAD v2.1 and 0.0478907 (4.78907%) in gnomAD v4.1, both above the BA1 threshold of 0.01 (1%), supporting BA1.
BS1Strong
BS1 · strong
The population frequency is also well above the strong benign threshold. The allele frequency is 0.0640054 in gnomAD v2.1 and 0.0478907 in gnomAD v4.1, both above the BS1 threshold of 0.003 (0.3%), so BS1 is met.
Recorded classification: Benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback.
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
62,124 / 1,297,204 alleles
gnomAD v4.1: 62,124 / 1,297,204 alleles. Recorded AF 0.0478907. Recorded homozygote count 1684.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0640054; MAF= 6.40054%, 2009/31388 alleles, homozygotes = 69) and has highest observed frequency in the African/African American population (AF= 0.0853042; MAF= 8.53042%, 743/8710 alleles, homozygotes = 34); grpmax FAF= 0.0802218.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 4 not met · 14 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The ANKRD26 c.-140C>G (NP_055730.2:p.?) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar as Benign.
This variant is common in population databases, with allele frequencies of 0.0640054 (6.40054%) in gnomAD v2.1 and 0.0478907 (4.78907%) in gnomAD v4.1, which are well above benign thresholds.
In silico splice prediction does not support a splice-altering effect, with a SpliceAI maximum delta score of 0.07.
No criteria match.
Met · 2
BA1 Stand aloneThis variant is far above the benign stand-alone population threshold. The allele frequency is 0.0640054 (6.40054%) in gnomAD v2.1 and 0.0478907 (4.78907%) in gnomAD v4.1, both above the BA1 threshold of 0.01 (1%), supporting BA1. Details ▾Hide ▴
Rule
BA1 applies when population frequency is greater than 1%.
Evidence considered
- gnomAD v2.1 total AF 0.0640054
- African/African American AF 0.0853042
- 69 homozygotes.
- gnomAD v4.1 total AF 0.0478907
- African/African American AF 0.0837021
- 1684 homozygotes.
Sources
BS1 StrongThe population frequency is also well above the strong benign threshold. The allele frequency is 0.0640054 in gnomAD v2.1 and 0.0478907 in gnomAD v4.1, both above the BS1 threshold of 0.003 (0.3%), so BS1 is met. Details ▾Hide ▴
Rule
BS1 applies when allele frequency is greater than expected for the disorder.
Evidence considered
- gnomAD v2.1 total AF 0.0640054
- grpmax FAF 0.0802218.
- gnomAD v4.1 total AF 0.0478907
- grpmax FAF 0.0818764.
Sources
Not met · 4 · evaluated, threshold not reached
PS4 This variant has not been observed in COSMIC and is listed in ClinVar as Benign; no case-control or enrichment data showing increased prevalence in affected individuals were identified, so PS4 is not met. Details ▾Hide ▴
Rule
PS4 requires statistically increased prevalence in affected individuals compared with controls.
Evidence considered
- ClinVar classification: Benign
- criteria provided
- single submitter
- 8 clinical laboratories.
- COSMIC search found no result for this variant.
Still missing
- Affected-versus-control enrichment data would be needed to support PS4.
Sources
clinvar ↗29927566
PM2 This variant is common in population databases rather than absent or rare. In gnomAD v2.1 the allele frequency is 0.0640054 (6.40054%), and in gnomAD v4.1 the allele frequency is 0.0478907 (4.78907%), both far above the usual rarity threshold of less than 0.001 for PM2, so PM2 is not met. Details ▾Hide ▴
Rule
PM2 supports pathogenicity only when the variant is absent or at extremely low frequency in population databases.
Evidence considered
- gnomAD v2.1 total AF 0.0640054
- 2009/31388 alleles
- 69 homozygotes.
- gnomAD v4.1 total AF 0.0478907
- 62124/1297204 alleles
- 1684 homozygotes.
Sources
PP3 Available computational evidence does not support a damaging effect on splicing. SpliceAI shows a maximum delta score of 0.07, which is below commonly used concern thresholds, so PP3 is not met. Details ▾Hide ▴
Rule
PP3 requires multiple computational predictions supporting a deleterious effect.
Evidence considered
- SpliceAI max delta score 0.07
- DS_DG 0.07
- all other delta scores 0.0.
Still missing
- If available
- validated regulatory prediction or functional data could further assess non-splice regulatory impact.
Sources
spliceai ↗31275557
BP4 SpliceAI predicts no significant splice impact, with a maximum delta score of 0.07, but this isolated splice prediction does not fully establish a benign effect for a 5'UTR regulatory variant. Therefore BP4 is not met. Details ▾Hide ▴
Rule
BP4 requires computational evidence supporting no impact on the gene or gene product.
Evidence considered
- SpliceAI max delta score 0.07.
Still missing
- Additional validated benign computational or functional evidence addressing regulatory impact would be needed.
Sources
spliceai ↗31275557
Not assessed · 14 · no assessment recorded
PS2 No confirmed de novo data with verified maternity and paternity were identified, so PS2 cannot be assessed. Details ▾Hide ▴
Rule
PS2 requires a confirmed de novo occurrence in a patient with the disease and no family history.
Still missing
- Confirmed de novo occurrence data are needed.
PS3 No validated functional studies demonstrating a damaging effect of this specific variant were identified from the available evidence, so PS3 was not assessed. Details ▾Hide ▴
Rule
PS3 requires well-established functional studies supportive of a damaging effect.
Still missing
- Well-established functional studies for NM_014915.2:c.-140C>G are needed.
Sources
2992756631275557
PM1 No established mutational hotspot or well-characterized critical functional region for applying PM1 to this specific 5'UTR position was identified in the available evidence. Details ▾Hide ▴
Rule
PM1 requires location in a mutational hotspot or critical functional domain without benign variation.
Still missing
- Variant-specific hotspot or critical-region evidence is needed.
PM3 No data were identified showing this variant in trans with a pathogenic variant in a recessive disorder, so PM3 was not assessed. Details ▾Hide ▴
Rule
PM3 requires detection in trans with a pathogenic variant for a recessive disorder.
Still missing
- Phase and recessive case data are needed.
PM6 No assumed de novo occurrence data were identified, so PM6 was not assessed. Details ▾Hide ▴
Rule
PM6 requires an assumed, but not confirmed, de novo occurrence.
Still missing
- Assumed de novo data are needed.
PP1 No segregation data were identified, so PP1 was not assessed. Details ▾Hide ▴
Rule
PP1 requires cosegregation with disease in multiple affected family members.
Still missing
- Family segregation data are needed.
PP4 No phenotype-specific evidence was identified showing a clinical presentation highly specific for a disorder caused by this variant, so PP4 was not assessed. Details ▾Hide ▴
Rule
PP4 requires a phenotype or family history highly specific for a disease with a single genetic etiology.
Still missing
- Detailed phenotype and differential-diagnosis data are needed.
PP5 Although ClinVar lists this variant as Benign, PP5 was not used because this criterion concerns pathogenic assertions from a reputable source and independent evidence is available. Details ▾Hide ▴
Rule
PP5 concerns pathogenic assertions from a reputable source without available primary evidence.
Evidence considered
- ClinVar classification: Benign.
Sources
BS2 Population databases show many homozygotes, but no direct evidence was identified confirming unaffected status in a setting appropriate for BS2, so this criterion was not assessed. Details ▾Hide ▴
Rule
BS2 requires observation in healthy adult individuals for a disorder with expected full penetrance at an early age.
Evidence considered
- 69 homozygotes in gnomAD v2.1.
- 1684 homozygotes in gnomAD v4.1.
Still missing
- Confirmed observation in healthy adults for the relevant disease context is needed.
Sources
BS3 No well-established functional studies demonstrating no damaging effect of this specific variant were formally curated in the available evidence for BS3 application. Details ▾Hide ▴
Rule
BS3 requires well-established functional studies showing no damaging effect.
Still missing
- Validated benign functional evidence for NM_014915.2:c.-140C>G is needed.
Sources
29927566
BS4 No segregation studies showing lack of cosegregation with disease were identified, so BS4 was not assessed. Details ▾Hide ▴
Rule
BS4 requires lack of segregation in affected family members.
Still missing
- Family segregation data demonstrating lack of cosegregation are needed.
BP2 No phase data were identified showing this variant in trans with a pathogenic variant for a dominant disorder or in cis with a pathogenic variant in any relevant setting, so BP2 was not assessed. Details ▾Hide ▴
Rule
BP2 requires phase information with another pathogenic variant.
Still missing
- Phase data are needed.
BP5 No alternate molecular explanation for the reported phenotype was identified from the available evidence, so BP5 was not assessed. Details ▾Hide ▴
Rule
BP5 requires a variant found in a case with an alternate molecular basis for disease.
Still missing
- A confirmed alternative cause of disease would be needed.
BP6 ClinVar reports this variant as Benign, but BP6 was not used because the submission is not from an expert panel and strong independent benign population evidence is already available. Details ▾Hide ▴
Rule
BP6 concerns benign assertions from a reputable source without available primary evidence.
Evidence considered
- ClinVar classification: Benign
- review status: criteria provided
- single submitter.
Sources
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AAlthough ANKRD26 has germline loss-of-function disease relevance, this 5'UTR substitution does not fall into the generic PVS1 null-variant categories such as nonsense, frameshift, or canonical +/-1,2 splice variants, so PVS1 is not applicable. Details ▾Hide ▴
Rule
Generic PVS1 fallback applies only to eligible loss-of-function variant classes.
Evidence considered
- ANKRD26 loss-of-function mechanism is supported at the gene level.
- NM_014915.2:c.-140C>G is a 5'UTR substitution outside the default generic PVS1 variant buckets.
Sources
pvs1_gene_contextpvs1_variant_assessment
PS1 N/APS1 is not applicable because this variant is in the 5'UTR and does not create the same amino acid change as a previously established pathogenic variant. Details ▾Hide ▴
Rule
PS1 requires the same amino acid change as a known pathogenic variant.
Evidence considered
- Variant consequence is noncoding 5'UTR.
PM4 N/APM4 is not applicable because this variant does not change protein length and is located in the 5'UTR. Details ▾Hide ▴
Rule
PM4 applies to protein length changes such as in-frame insertions/deletions or stop-loss variants.
Evidence considered
- Variant consequence is noncoding 5'UTR.
PM5 N/APM5 is not applicable because this variant is in the 5'UTR and does not alter an amino acid residue where a different pathogenic missense change has been established. Details ▾Hide ▴
Rule
PM5 applies to novel missense changes at an amino acid residue with a different pathogenic missense variant.
Evidence considered
- Variant consequence is noncoding 5'UTR.
PP2 N/APP2 is not applicable because this is not a missense variant. Details ▾Hide ▴
Rule
PP2 is a missense-specific criterion.
Evidence considered
- Variant consequence is noncoding 5'UTR.
BP1 N/ABP1 is not applicable because this is not a missense variant. Details ▾Hide ▴
Rule
BP1 is a missense-specific criterion.
Evidence considered
- Variant consequence is noncoding 5'UTR.
BP3 N/ABP3 is not applicable because this is not an in-frame insertion or deletion in a repetitive region. Details ▾Hide ▴
Rule
BP3 applies to certain in-frame insertions/deletions in repetitive regions without known function.
Evidence considered
- Variant consequence is a single-nucleotide 5'UTR substitution.
BP7 N/ABP7 is not applicable because this variant is not a synonymous or intronic change outside splice regions; it is a 5'UTR substitution. Details ▾Hide ▴
Rule
BP7 applies to synonymous or certain intronic variants with no predicted splice impact.
Evidence considered
- Variant consequence is noncoding 5'UTR.
Identifiers
- Gene
- ANKRD26
- Transcript
- NM_014915.2
- Coding (HGVS c.)
- NM_014915.2:c.-140C>G
- Protein (HGVS p.)
- NP_055730.2:p.?
- GRCh38
- chr10:27100466 G>C
- GRCh37
- chr10:27389395 G>C
Gene diagram
Every interpreted variant in ANKRD26, mapped onto the exon structure of NM_014915.2. Select a row to find it on the plot.
ANKRD26NM_014915.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in ANKRD26
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
62,124 / 1,297,204 alleles
AF 0.0479 · 1684 homozygotes · FAF 0.0819
gnomAD v2.1
2,009 / 31,388 alleles
AF 0.064 · 69 homozygotes · FAF 0.0802
By genetic ancestry
gnomAD v4.1
AF 0.048 · 62124 / 1,297,204 alleles · 1684 hom · FAF 0.082
| African/African American5637 / 67,346 | 0.084245 hom |
| Ashkenazi Jewish1595 / 22,702 | 0.0742 hom |
| European (Finnish)2280 / 42,134 | 0.05453 hom |
| European (non-Finnish)46842 / 960,288 | 0.0491212 hom |
| Remaining individuals2409 / 51,146 | 0.04756 hom |
| Middle Eastern162 / 3,700 | 0.0446 hom |
| South Asian2093 / 69,972 | 0.0353 hom |
| Admixed American1007 / 38,008 | 0.02615 hom |
| Amish20 / 908 | 0.0221 hom |
| East Asian79 / 41,000 | 0.00191 hom |
gnomAD v2.1
AF 0.064 · 2009 / 31,388 alleles · 69 hom · FAF 0.08
| African/African American743 / 8,710 | 0.08534 hom |
| Ashkenazi Jewish22 / 288 | 0.076 |
| Remaining individuals71 / 1,088 | 0.0652 hom |
| European (non-Finnish)957 / 15,420 | 0.06226 hom |
| European (Finnish)191 / 3,474 | 0.0557 hom |
| Admixed American21 / 848 | 0.025 |
| East Asian4 / 1,560 | 0.0026 |
0 alternate alleles recorded in 1 other group: South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0478907; MAF= 4.78907%, 62124/1297204 alleles, homozygotes = 1684) and has highest observed frequency in the African/African American population (AF= 0.0837021; MAF= 8.37021%, 5637/67346 alleles, homozygotes = 245); grpmax FAF= 0.0818764.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0640054; MAF= 6.40054%, 2009/31388 alleles, homozygotes = 69) and has highest observed frequency in the African/African American population (AF= 0.0853042; MAF= 8.53042%, 743/8710 alleles, homozygotes = 34); grpmax FAF= 0.0802218.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Available computational evidence does not support a damaging effect on splicing. SpliceAI shows a maximum delta score of 0.07, which is below commonly used concern thresholds, so PP3 is not met. Details ▾Hide ▴
Rule
PP3 requires multiple computational predictions supporting a deleterious effect.
Evidence considered
- SpliceAI max delta score 0.07
- DS_DG 0.07
- all other delta scores 0.0.
Still missing
- If available
- validated regulatory prediction or functional data could further assess non-splice regulatory impact.
Sources
spliceai ↗31275557
BP4 SpliceAI predicts no significant splice impact, with a maximum delta score of 0.07, but this isolated splice prediction does not fully establish a benign effect for a 5'UTR regulatory variant. Therefore BP4 is not met. Details ▾Hide ▴
Rule
BP4 requires computational evidence supporting no impact on the gene or gene product.
Evidence considered
- SpliceAI max delta score 0.07.
Still missing
- Additional validated benign computational or functional evidence addressing regulatory impact would be needed.
Sources
spliceai ↗31275557
BP7 N/ABP7 is not applicable because this variant is not a synonymous or intronic change outside splice regions; it is a 5'UTR substitution. Details ▾Hide ▴
Rule
BP7 applies to synonymous or certain intronic variants with no predicted splice impact.
Evidence considered
- Variant consequence is noncoding 5'UTR.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
62,124 / 1,297,204 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/260453/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-27389395-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-27100466-G-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_014915.2%3Ac.-140…
- OncoKB ↗www.oncokb.org/gene/ANKRD26/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=ANKRD26+c.-140C%3EG
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= 0.0478907; MAF= 4.78907%, 62124/1297204 alleles, homozygotes = 1684) and has highest observed frequency in the African/African American population (AF= 0.0837021; MAF= 8.37021%, 5637/67346 alleles, homozygotes = 245); grpmax FAF= 0.0818764.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0640054; MAF= 6.40054%, 2009/31388 alleles, homozygotes = 69) and has highest observed frequency in the African/African American population (AF= 0.0853042; MAF= 8.53042%, 743/8710 alleles, homozygotes = 34); grpmax FAF= 0.0802218.
ClinVar
This variant has been reported in ClinVar as Benign (8 clinical laboratories).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).