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.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.MYCN is a transcription factor that controls the expression of genes involved in cell growth, division, survival, and metabolism. It is normally active mainly during embryonic development and is largely restricted to cells of the nervous system and a few other tissues. Amplification of MYCN drives cancer, most notably neuroblastoma, and is also seen in medulloblastoma, glioblastoma, and other solid tumors such as breast and small cell lung cancers.
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met (supporting): absent from gnomAD-Canada with maximum allele frequency 8.8e-06, far below the 0.1% threshold, and no homozygotes.
Met (supporting): REVEL 0.05 (below the 0.183 threshold) and SpliceAI max delta 0.006 (below 0.2) both predict no damaging effect.
Uncertain significance: one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) do not reach any classification threshold under generic ACMG/AMP 2015 rules.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 4 / 1,614,030 alleles. Recorded AF 2.47827e-06. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 3.97801e-06; MAF= 0.00040%, 1/251382 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79477e-06; MAF= 0.00088%, 1/113704 alleles, homozygotes = 0).
Absent from gnomAD-Canada v1.0.
Recorded REVEL score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.
A ClinVar laboratory submission summary was not recorded.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MYCN, a transcription factor, is altered by amplification and overexpression in a variety of cancer types including in neuroblastoma.
This variant has previously been reported in somatic cancers (COSMIC; COSV107256643, n = 1 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 6 not met · 15 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
No MYCN CSPEC/VCEP specification is available for this case (framework_mode=generic_acmg, cspec.found=false), so generic ACMG/AMP definitions were applied for all codon/residue/domain criteria.
The variant NM_005378.5:c.868A>G / p.(Asn290Asp) is absent from ClinVar, so no same-variant or same-amino-acid-change comparator classification exists to anchor PS1 or PM5.
The pipeline's automated PM5 same-residue harvesting step explicitly declined to run, leaving PM5 unassessed pending manual review.
A cancer hotspot database lookup found no statistically significant hotspot at MYCN N290, and no functional domain boundary table for MYCN was available, so PM1 was scored not_met on the basis of absent supporting evidence.
No missense constraint or disease-mechanism data for MYCN was present in the bundle, so PP2 and BP1 (which are mechanism-dependent and require opposite conclusions from the same underlying data) were both left not_assessed rather than inferred.
No applicable MYCN-specific VCEP or gene-specific framework was retrieved; generic ACMG/AMP criteria were used.
The available case-evidence bundle contains no proband, parental, pedigree, meiosis, affected-relative, or unaffected-relative segregation data, so PS2, PM6, PP1, and BS4 are all not assessed.
No publication was reviewed because the literature pass contained no PMIDs and no relevant full-text publication was available for these criteria.
MYCN has no ClinGen CSPEC/VCEP specification available (cspec.found=false; vcep_materials.note='no cspec url available'); generic ACMG/AMP framework applies, but generic ACMG PS3/BS3 both require validated functional studies, none of which were located for this specific variant.
The case evidence bundle (prefetch, evidence, literature_pass, vcep_materials, fulltext_map) contains no functional assay results (e.g., transactivation, transcriptional activity, proliferation, degradation/stability, phosphorylation) for NM_005378.5:c.868A>G / p.Asn290Asp.
Literature identified via the PVS1 gene-context search (Feingold syndrome, megalencephaly-polydactyly reports) is disease-association/case-report literature, not functional assay literature, and none of it mentions this specific variant.
No gene-specific ClinGen VCEP specification exists for MYCN in this case (cspec.found=false; framework_mode=generic_acmg), so generic ACMG/AMP calibrated computational-evidence thresholds were applied.
Variant is missense (p.Asn290Asp), not synonymous, so BP7 is not applicable and was not assessed.
REVEL (0.05) and SpliceAI (max delta 0.006) both indicate no damaging/splice-altering effect, converging on BP4_Supporting; PP3 was correspondingly assessed as not_met to avoid double counting the same underlying prediction direction across PP3/BP4.
BayesDel score was available in prefetch data but excluded from all criteria per pipeline policy: no verified published calibration threshold/publication for BayesDel is available.
No MYCN-specific ClinGen CSPEC/VCEP framework was available, so generic ACMG/AMP population rules were used.
Population data support PM2 at supporting strength because the variant is ultra-rare and has no observed homozygotes, but do not support BA1 or BS1.
BS2 was not assessed because aggregate population homozygote counts do not establish healthy status, penetrance, or inheritance-consistent non-disease observations.
No criteria match.
PM2 is met at supporting strength. The variant is absent from gnomAD-Canada and occurs only at an ultra-rare frequency in gnomAD v2.1 and v4.1, with no homozygotes. The maximum observed allele frequency is 8.79477e-06, far below the generic rare-variant threshold of 0.1% used here when no applicable MYCN-specific specification is available.
Generic ACMG/AMP PM2: absent or extremely rare in population databases; for this non-VCEP assessment, supporting evidence is assigned when the maximum observed allele frequency is below 0.1%, with no homozygotes and no applicable gene-specific specification.
No governing ClinGen VCEP specification was found for MYCN (cspec.found=false; framework_mode=generic_acmg), so generic ACMG/AMP calibrated in-silico evidence applies. Two independent, convergent computational lines of evidence support a benign/no-impact prediction for this missense variant: (1) REVEL score = 0.05, below the ClinGen SVI-calibrated BP4_Supporting threshold of <=0.183 for REVEL (Pejaver et al. 2022, PMID:36413997); (2) SpliceAI predicts no meaningful splice impact (max delta score = 0.006), well below the 0.2 threshold for splice-altering predictions established by Jaganathan et al. 2019 (PMID:30661751). Both lines of evidence are consistent in direction (no damaging effect) and are combined into a single BP4 application at supporting strength; they are not stacked to increase strength beyond supporting, and PP3 is correspondingly not met for the same variant to avoid double counting. BayesDel score was available but excluded because no verified published calibration threshold is available to this pipeline for BayesDel.
PM1 requires the variant to fall within a mutational hotspot and/or a critical, well-established functional domain lacking benign variation. A dedicated cancer hotspot lookup for MYCN N290 returned no result, with the evidence sentence explicitly stating the variant does not lie in a statistically significant hotspot. No MYCN CSPEC/VCEP is available to define approved critical functional domain boundaries (e.g., Myc Box regions or the C-terminal bHLH-Zip dimerization/DNA-binding domain), and OncoKB provided only gene-level (not variant- or domain-specific) functional context, explicitly noting no variant-specific reviewed functional evidence. Without an authoritative domain map or hotspot signal, there is no positive evidence supporting PM1 for residue 290.
NM_005378.5:c.868A>G (p.Asn290Asp) is a missense variant. No governing ClinGen VCEP specification was found for MYCN (cspec.found=false; framework_mode=generic_acmg), so generic ACMG/AMP calibrated in-silico evidence applies. REVEL score is 0.05, well below the ClinGen SVI-calibrated PP3 supporting threshold (REVEL >=0.644, per Pejaver et al. 2022, PMID:36413997), so REVEL does not support a damaging prediction. SpliceAI predicts no splice impact (max delta score = 0.006, DS_AG=0.00, DS_AL=0.006, DS_DG=0.001, DS_DL=0.00), far below the 0.2 threshold established as splice-altering by Jaganathan et al. 2019 (PMID:30661751). BayesDel score (-0.75139) is available but has no verified published calibration threshold available to this pipeline and is therefore not usable as PP3/BP4 evidence. No aGVGD/Align-GVGD score was available (hci_prior.found=false). No gene-specific VCEP PP3/BP4 lookup material exists for this case. Neither computational path (missense or splice) supports a damaging prediction, so PP3 is not met.
PP5 is not met. The exact variant NM_005378.5:c.868A>G is reported as absent from ClinVar, with no variation ID, classification, review status, or expert-panel assertion. Therefore, there is no exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification to support PP5.
Apply PP5 at supporting strength only for an exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic classification; ordinary laboratory submissions, aggregate labels, and non-expert assertions do not qualify.
BA1 is not met. The maximum observed allele frequency is far below the generic stand-alone benign threshold of greater than 1%: gnomAD v4.1 total AF is 2.47827e-06, with maximum population AF 3.38973e-06 and group maximum FAF 7.9e-07; gnomAD v2.1 total AF is 3.97801e-06.
Generic ACMG/AMP BA1: stand-alone benign evidence requires an allele frequency greater than 1% in a population database, absent a more applicable gene-specific specification.
BS1 is not met. The variant is present only at ultra-rare frequencies in gnomAD and is well below the generic population-frequency threshold used for a benign frequency greater than expected for a rare Mendelian disorder. There is no evidence that its frequency exceeds a disease-specific maximum credible allele frequency.
Generic ACMG/AMP BS1: allele frequency is greater than expected for the disorder; in this assessment, the generic rare-disease screening threshold is greater than 0.3% when no gene-specific maximum credible allele frequency is available.
BP6 is not met. The exact variant NM_005378.5:c.868A>G is reported as absent from ClinVar, with no variation ID, classification, review status, or expert-panel assertion. Therefore, there is no exact-variant ClinVar expert-panel Benign or Likely benign classification to support BP6.
Apply BP6 at supporting strength only for an exact-variant ClinVar expert-panel Benign or Likely benign classification; ordinary laboratory submissions, aggregate labels, and non-expert assertions do not qualify.
PS1 requires identifying an alternate nucleotide change that produces the identical amino-acid substitution p.(Asn290Asp) and is already classified pathogenic/likely pathogenic by ClinVar or established literature. No such comparator search was performed in this evidence bundle: the only ClinVar query executed targeted the exact variant NM_005378.5:c.868A>G itself (not other codon changes yielding p.Asn290Asp) and returned no result (variant absent from ClinVar). No CSPEC/VCEP for MYCN was found (cspec.found = false), and no literature hits were retrieved (literature_pass.json: total_pmids = 0). There is therefore no basis in the assembled evidence to confirm or refute a same-amino-acid-change pathogenic comparator.
No case-level parental testing, trio result, maternity/paternity confirmation, or other evidence establishing that NM_005378.5:c.868A>G arose de novo in the proband is provided. The criterion cannot be assessed.
Generic ACMG/AMP PS2 requires confirmed de novo occurrence in the patient with confirmed maternity/paternity; strength may be increased only when the phenotype is highly specific and/or additional validated de novo observations support it.
No validated functional/biochemical assay data for NM_005378.5:c.868A>G (p.Asn290Asp) were found in this case's evidence bundle. There is no ClinGen CSPEC/VCEP for MYCN (cspec.found=false, vcep_materials empty), no ClinVar record, and no PMIDs were returned by the literature pass (literature_packet.total_pmids=0; literature_pass.json note='No PMIDs found across evidence sources'). The PVS1 gene-context literature search surfaced disease-association case reports (Feingold syndrome / megalencephaly-polydactyly syndrome papers) but none report a validated functional assay (e.g., transactivation, proliferation, degradation, phosphorylation) characterizing this specific variant or its exact residue. OncoKB and COSMIC provide only gene/cancer-context annotations, not variant-specific functional assay results. No well-established, publication-cited computational threshold applicable to PS3 (this criterion requires wet-lab/functional assay evidence, not predictor scores) was available either. Absent any assay evidence meeting validation standards, PS3 cannot be assessed.
No case-control dataset, affected-case count, statistical enrichment, or variant-specific disease-cohort evidence is available for NM_005378.5:c.868A>G (NP_005369.2:p.Asn290Asp). The available records do not support assessing PS4.
Generic ACMG/AMP PS4 requires statistically significant enrichment of the variant in affected individuals compared with controls, or an adequately supported case series when applicable; no applicable MYCN-specific VCEP rule was available.
PM5 requires identifying a different missense change at the same residue (position 290) previously established as pathogenic. The pipeline's dedicated PM5 candidate-harvesting step explicitly declined to run an automated same-residue ClinVar search, flagging 'Unable to confirm classic same-residue PM5 semantics safely; skipping automatic candidate harvesting' and returning eligible_for_classic_pm5_search=false with zero candidates collected. No manual same-residue search results are present elsewhere in the evidence bundle.
No case-level report of NM_005378.5:c.868A>G as presumed de novo without confirmed maternity/paternity is available. The criterion cannot be assessed.
Generic ACMG/AMP PM6 may be applied for a presumed de novo variant when maternity and paternity are not confirmed, but the proband phenotype and parental testing must still be documented; it is weaker than PS2.
No affected relatives, informative meioses, family structure, phenotype segregation data, or genotype results from relatives are provided. Therefore, cosegregation cannot be evaluated and PP1 cannot be assigned.
Generic ACMG/AMP PP1 requires cosegregation of the variant with disease in multiple affected family members; strength can be increased only with sufficient informative meioses and appropriate phenotype specificity.
PP2 requires the gene to have a low rate of benign missense variation and missense to be an established common disease mechanism. This evidence bundle contains no missense constraint metric (e.g., gene-level missense Z-score/observed-vs-expected data), no MYCN CSPEC/VCEP mechanism statement, and no literature characterizing the proportion of MYCN germline disease-causing variants that are missense versus loss-of-function. OncoKB context describes MYCN somatic oncogenic activity via amplification/overexpression, not point-mutation mechanism, and is gene-level/non-variant-specific. Absent a grounded source in this bundle addressing MYCN's germline missense disease mechanism, PP2 cannot be confidently assessed either way.
The case bundle provides no patient phenotype, clinical diagnosis, or phenotype-to-disease specificity assessment for this variant. Gene-level descriptions of MYCN-associated disease and cancer biology are not sufficient to establish PP4.
Generic ACMG/AMP PP4 may be applied only when the patient's phenotype or family history is highly specific for a disease with a single genetic etiology; gene-level context alone is insufficient.
BS2 cannot be established from the available population data. gnomAD reports zero homozygotes, but absence of homozygotes is not evidence that the variant was observed in healthy adults or in unaffected individuals with an inheritance pattern that would contradict disease causality. No phenotype-annotated healthy-carrier or affected-status dataset was provided.
Generic ACMG/AMP BS2: the variant is observed in healthy adults for a fully penetrant dominant disorder, or in healthy adults in the homozygous or hemizygous state for a recessive disorder; a raw population homozygote count without phenotype and inheritance context is insufficient.
No functional/biochemical assay data demonstrating normal (wild-type-like) protein function for NM_005378.5:c.868A>G (p.Asn290Asp) were found in this case's evidence bundle. As with PS3, there is no ClinGen CSPEC/VCEP for MYCN, no ClinVar record, and the literature pass returned zero PMIDs. No source in the bundle reports a validated assay result for this variant, whether damaging or benign. Absent any assay evidence, BS3 cannot be assessed.
No unaffected relatives with reliable phenotyping and confirmed absence of the variant are documented. Non-segregation cannot be evaluated and BS4 cannot be assigned.
Generic ACMG/AMP BS4 requires lack of segregation in clinically unaffected members of a family with an appropriate phenotype and adequate ascertainment; absence of family data is insufficient for BS4.
BP1 requires the gene to have an established disease mechanism where missense variants are not a common cause of disease (i.e., primarily truncating/LOF-driven). This evidence bundle contains no missense constraint metric, no MYCN CSPEC/VCEP mechanism statement, and no literature-based characterization of the MYCN germline disease mechanism spectrum needed to determine whether missense variants are generally benign in this gene. This is the same evidentiary gap identified for PP2, so BP1 also cannot be confidently assessed from the available sources.
BP2 requires observation of the variant in trans with a pathogenic or likely pathogenic variant in an affected individual for a dominant disorder, or in cis with a pathogenic variant for a recessive disorder. The case bundle contains no affected-proband genotype, second-variant result, or phase information. BP2 cannot be assessed.
Generic ACMG/AMP BP2: variant observed in trans with a pathogenic variant in an affected individual with a dominant disorder, or in cis with a pathogenic variant in a recessive disorder; phase and affected-individual evidence are required.
BP5 cannot be assessed because the case bundle does not provide a patient diagnosis, an established molecular explanation for the phenotype, or evidence that another variant explains the relevant disease. Somatic cancer database context and gene-level MYCN information do not establish an alternate molecular cause for this case.
Generic ACMG/AMP BP5 requires a benign explanation for the patient's phenotype by another molecular cause; absence of case-level diagnostic and alternate-variant evidence prevents assessment.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_005378.5:c.868A>G in MYCN is a missense substitution predicted to produce NP_005369.2:p.(Asn290Asp). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication, because no structured VCEP criteria-combination framework governs this case (framework_complete=false); the generic ACMG/AMP 2015 fallback applies.
deterministic_prefilter: requires_null_variant_class
PM3 is intended for pathogenic variants observed in trans with another pathogenic or likely pathogenic variant in an affected individual with a recessive disorder. The available MYCN disease context supports autosomal-dominant germline disorders (including Feingold syndrome type 1 and MYCN-related megalencephaly-polydactyly syndrome), and no recessive MYCN inheritance framework is provided. PM3 is therefore not applicable to this case.
Generic ACMG/AMP PM3: pathogenic or likely pathogenic variant observed in trans with a pathogenic variant for a recessive disorder; not applicable when the relevant disorder is dominantly inherited.
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_005378.5:c.868A>G in MYCN is a missense substitution predicted to produce NP_005369.2:p.(Asn290Asp). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication, because no structured VCEP criteria-combination framework governs this case (framework_complete=false); the generic ACMG/AMP 2015 fallback applies.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_005378.5:c.868A>G in MYCN is a missense substitution predicted to produce NP_005369.2:p.(Asn290Asp). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication, because no structured VCEP criteria-combination framework governs this case (framework_complete=false); the generic ACMG/AMP 2015 fallback applies.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_005378.5:c.868A>G in MYCN is a missense substitution predicted to produce NP_005369.2:p.(Asn290Asp). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication, because no structured VCEP criteria-combination framework governs this case (framework_complete=false); the generic ACMG/AMP 2015 fallback applies.
deterministic_prefilter: requires_synonymous
Every interpreted variant in MYCN, mapped onto the exon structure of NM_005378.5. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| European (non-Finnish)4 / 1,180,036 | 3.4e-06 |
| European (non-Finnish)1 / 113,704 | 8.8e-06 |
This variant is present in gnomAD v4.1 (AF= 2.47827e-06; MAF= 0.00025%, 4/1614030 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.38973e-06; MAF= 0.00034%, 4/1180036 alleles, homozygotes = 0); grpmax FAF= 7.9e-07.
This variant is present in gnomAD v2.1 (AF= 3.97801e-06; MAF= 0.00040%, 1/251382 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79477e-06; MAF= 0.00088%, 1/113704 alleles, homozygotes = 0).
Absent from gnomAD-Canada v1.0.
No governing ClinGen VCEP specification was found for MYCN (cspec.found=false; framework_mode=generic_acmg), so generic ACMG/AMP calibrated in-silico evidence applies. Two independent, convergent computational lines of evidence support a benign/no-impact prediction for this missense variant: (1) REVEL score = 0.05, below the ClinGen SVI-calibrated BP4_Supporting threshold of <=0.183 for REVEL (Pejaver et al. 2022, PMID:36413997); (2) SpliceAI predicts no meaningful splice impact (max delta score = 0.006), well below the 0.2 threshold for splice-altering predictions established by Jaganathan et al. 2019 (PMID:30661751). Both lines of evidence are consistent in direction (no damaging effect) and are combined into a single BP4 application at supporting strength; they are not stacked to increase strength beyond supporting, and PP3 is correspondingly not met for the same variant to avoid double counting. BayesDel score was available but excluded because no verified published calibration threshold is available to this pipeline for BayesDel.
NM_005378.5:c.868A>G (p.Asn290Asp) is a missense variant. No governing ClinGen VCEP specification was found for MYCN (cspec.found=false; framework_mode=generic_acmg), so generic ACMG/AMP calibrated in-silico evidence applies. REVEL score is 0.05, well below the ClinGen SVI-calibrated PP3 supporting threshold (REVEL >=0.644, per Pejaver et al. 2022, PMID:36413997), so REVEL does not support a damaging prediction. SpliceAI predicts no splice impact (max delta score = 0.006, DS_AG=0.00, DS_AL=0.006, DS_DG=0.001, DS_DL=0.00), far below the 0.2 threshold established as splice-altering by Jaganathan et al. 2019 (PMID:30661751). BayesDel score (-0.75139) is available but has no verified published calibration threshold available to this pipeline and is therefore not usable as PP3/BP4 evidence. No aGVGD/Align-GVGD score was available (hci_prior.found=false). No gene-specific VCEP PP3/BP4 lookup material exists for this case. Neither computational path (missense or splice) supports a damaging prediction, so PP3 is not met.
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_005378.5:c.868A>G in MYCN is a missense substitution predicted to produce NP_005369.2:p.(Asn290Asp). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication, because no structured VCEP criteria-combination framework governs this case (framework_complete=false); the generic ACMG/AMP 2015 fallback applies.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.05. BayesDel score = -0.75139.
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.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 2.47827e-06; MAF= 0.00025%, 4/1614030 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.38973e-06; MAF= 0.00034%, 4/1180036 alleles, homozygotes = 0); grpmax FAF= 7.9e-07.
This variant is present in gnomAD v2.1 (AF= 3.97801e-06; MAF= 0.00040%, 1/251382 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79477e-06; MAF= 0.00088%, 1/113704 alleles, homozygotes = 0).
Absent from gnomAD-Canada v1.0.
This variant is absent from ClinVar.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.05. BayesDel score = -0.75139.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MYCN, a transcription factor, is altered by amplification and overexpression in a variety of cancer types including in neuroblastoma.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV107256643, n = 1 times).
This variant does not lie in a statistically significant hotspot.