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.BRIP1 encodes a helicase enzyme that partners with the BRCA1 protein to repair double-strand breaks in DNA, a process essential for maintaining genome stability. Germline mutations in this gene predispose carriers to ovarian cancer, and inheriting two faulty copies causes Fanconi anemia complementation group J, a rare disorder of impaired DNA repair. BRIP1 acts as a tumor suppressor, so loss of its function raises cancer risk, particularly in the ovary.
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): gnomAD v4.1 total allele frequency is 2.66e-05 (43/1,613,968), below the 0.1% PM2 threshold.
Met (moderate): REVEL score 0.804 falls in the ClinGen-calibrated Pathogenic Moderate band (>=0.773).
No benign criterion marked as applied in the recorded assessment.
No BRIP1-specific framework exists, so generic ACMG/AMP 2015 rules applied; only PM2 (supporting) and PP3 (moderate) were met, satisfying no combining rule, yielding a classification of VUS.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 43 / 1,613,968 alleles. Recorded AF 2.66424e-05. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 2.83968e-05; MAF= 0.00284%, 8/281722 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.01354e-05; MAF= 0.00501%, 1/19946 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
Absent from gnomAD-Canada v1.0.
Recorded REVEL score: 0.804. Refer to the recorded PP3/BP4 rationale for interpretation.
15 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
This variant has previously been reported in somatic cancers (COSMIC; COSV51997487, n = 5 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 · 7 not met · 15 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
No official ClinGen VCEP/CSPEC exists for BRIP1 (framework_mode=generic_acmg, cspec.found=false); generic ACMG/AMP 2015 criteria were applied for all five criteria in this group.
The case's pm5_candidates.json artifact explicitly declined automatic same-residue harvesting, leaving PM5 (and by extension PS1, which also depends on same-residue/same-change comparator data) without sufficient supporting data to assess as met or not_met.
PMID:31822495 (functional characterization of BRIP1 missense variants in the helicase domain) was the only source found bearing directly on domain/mechanism criteria (PM1, PP2, BP1) and was read in full text for this reason.
Cancerhotspots.org was directly queried for BRIP1 R865 and returned no statistically significant hotspot, supporting a not_met call for PM1.
No missense constraint metric (gnomAD missense Z-score / o:e) was available in the bundle to complete the second required element of PP2, so PP2 was left not_assessed rather than inferred.
PS3 and BS3 both require validated functional assay data for the specific variant; none was located in the case bundle, prefetch, evidence.json, or in full-text search of all cited publications (searched for '865', 'Arg865', 'R865W', 'p.R865' — no matches in any retrieved full text).
No BRIP1-specific ClinGen VCEP CSPEC or PP3/BP4 lookup spreadsheet is present in this case (cspec.found=false; vcep_materials files_found=[]); generic ACMG/AMP calibrated in-silico thresholds were applied.
REVEL = 0.804 meets the ClinGen SVI (Pejaver 2022, PMID 36413997) Pathogenic-Moderate calibration band (>=0.773), supporting PP3 at moderate strength for this missense variant.
BayesDel (0.398139) was retrieved but excluded from PP3/BP4 determination per pipeline policy: no verified published calibration threshold/PMID is available for BayesDel.
SpliceAI max delta = 0.066 shows no splice-disrupting signal; this is a neutral/non-contributory finding for a missense variant and does not itself support either PP3 or BP4.
BP7 is not applicable — the variant is missense (p.Arg865Trp), not synonymous.
No criteria match.
No BRIP1 VCEP/ClinGen gene-specific specification was retrieved. The variant is present but extremely rare across gnomAD releases: v4.1 total AF 2.66424e-05 (43/1,613,968), highest major ancestry-group AF 3.2941e-05 (South Asian), and v2.1 total AF 2.83968e-05. All are below the generic non-VCEP PM2 operating threshold of 0.1%; PM2 is met at supporting strength. The observed alleles and absence of homozygotes do not constitute benign frequency evidence.
generic_non_vcep_population_operating_threshold: PM2_supporting for AF <0.1%
NM_032043.3:c.2593C>T (p.Arg865Trp) is a missense variant. No governing VCEP/CSPEC is available for BRIP1 (cspec.found=false; vcep_materials.final_classification_framework.found=false, framework falls back to generic ACMG/AMP 2015), and no gene-specific PP3/BP4 lookup spreadsheet was provided, so the generic calibrated in-silico approach applies. REVEL score = 0.804, which falls within the ClinGen SVI (Pejaver et al. 2022, PMID 36413997) calibrated 'Pathogenic Moderate' band (REVEL >= 0.773) for missense in-silico evidence, supporting PP3 at moderate strength. BayesDel score (0.398139) was also computed but is not used to support or contradict this call: no verified published calibration threshold/PMID for BayesDel is available to this pipeline, so per policy it is treated as not_available regardless of the raw score. SpliceAI predicts no meaningful splice disruption (max delta score = 0.066, well below any splice-altering threshold), so the splice-impact path is silent/non-contributory here (neither supports nor conflicts with the missense PP3 call) and is not itself sufficient to invoke PP3 via splicing. Align-GVGD/HCI prior data were not available for this variant (hci_prior.found=false).
REVEL >= 0.773 (ClinGen SVI Pejaver 2022 calibration, PMID 36413997) => PP3_Moderate for missense variant with no applicable VCEP override
No ClinGen VCEP/CSPEC exists for BRIP1, so generic ACMG PM1 was applied. Cancerhotspots.org was queried directly for 'BRIP1 R865' and explicitly returned no statistically significant hotspot at this residue. PMID:31822495 describes p.Arg865Trp as falling within the broad, 888-amino-acid BRIP1 helicase domain, but that domain is not characterized as free of benign missense variation -- the paper explicitly documents a mix of wildtype-like, hypomorphic, and null missense alleles scattered across the same domain, and residue 865 itself is not identified as one of the seven conserved DEAH helicase motifs, the Fe-S binding cluster, or any other discretely critical subregion. No mutational cluster or case-control enrichment statistic specific to residue 865 was found.
The exact-variant ClinVar record has no expert-panel submissions and is classified as uncertain significance by laboratory submitters. It does not meet the required exact-variant ClinVar expert-panel Pathogenic/Likely pathogenic condition for PP5.
Apply PP5 only for an exact-variant ClinVar expert-panel Pathogenic or Likely pathogenic assertion.
No BRIP1 VCEP/ClinGen gene-specific specification was retrieved, so generic ACMG/AMP population-frequency logic applies. The highest robust gnomAD v4.1 population AF is 3.2941e-05 (South Asian; 3/91,072 alleles), with grpmax filtering allele frequency 2.314e-05. These values are far below the generic BA1 stand-alone benign frequency threshold of 5%; BA1 is not met.
generic_acmg_amp: BA1 requires allele frequency >5% in an appropriate population dataset
No BRIP1 VCEP/ClinGen gene-specific frequency threshold was retrieved. Under the generic non-VCEP operating threshold (BS1 >0.3%), the observed gnomAD frequencies are much lower: v4.1 total AF 2.66424e-05, highest major ancestry-group AF 3.2941e-05, and grpmax FAF 2.314e-05. BS1 is not met.
generic_non_vcep_population_operating_threshold: BS1 requires AF >0.3%
No ClinGen VCEP/CSPEC exists for BRIP1, so generic ACMG BP1 was applied. BP1 requires that the gene's disease mechanism is exclusively or predominantly via truncating/loss-of-function variants such that missense variants are not expected to be pathogenic. PMID:31822495 directly contradicts this premise: it functionally demonstrates that specific BRIP1 missense substitutions (A349P, P47A, G690E, D791V and others) cause loss-of-function or hypomorphic ICL-repair defects and are enriched among breast/ovarian cancer patients relative to population controls, confirming missense variation is an established BRIP1 pathogenic mechanism. BP1 is therefore not met for this gene.
The calibrated missense in-silico predictor (REVEL = 0.804) falls in the Pathogenic-Moderate range per ClinGen SVI calibration (PMID 36413997), i.e. in the pathogenic direction, not the benign direction, so BP4 cannot be applied for the missense path. SpliceAI shows no splice disruption (max delta = 0.066), which is simply an absence of a splicing signal for this missense variant rather than an independent benign in-silico protein-effect prediction, and is not sufficient on its own to invoke BP4 for a missense variant already showing a pathogenic-direction missense score. No VCEP-specific PP3/BP4 lookup override exists for BRIP1 to redirect this call.
REVEL >= 0.773 excludes BP4 under the missense in-silico path; SpliceAI absence-of-effect alone is insufficient for BP4 in a missense variant already carrying a pathogenic-direction predictor score
The exact-variant ClinVar record has no expert-panel submissions and no Benign/Likely benign expert-panel assertion. It therefore does not meet the required condition for BP6.
Apply BP6 only for an exact-variant ClinVar expert-panel Benign or Likely benign assertion.
No ClinGen VCEP/CSPEC exists for BRIP1 (cspec.found=false; framework_mode=generic_acmg), so generic ACMG PS1 applies. PS1 requires a different nucleotide change producing the identical amino acid change (p.Arg865Trp) already established as pathogenic. No such comparator variant is present anywhere in the case bundle, ClinVar criterion-lead PMID trail, or PM5 candidate scan.
Not assessed: the case bundle contains no proband phenotype, parental genotypes, or parentage confirmation for BRIP1 c.2593C>T (p.Arg865Trp).
Generic ACMG/AMP 2015 de novo criterion (PS2); no BRIP1 VCEP/CSPEC was retrieved.
No gene-specific VCEP/CSPEC was found for BRIP1 in this case (framework_mode = generic_acmg, cspec.found = false), so generic ACMG applies. Searched all full-text cited publications (PMID:31822495, PMID:29368626, PMID:25741868, PMID:26467025, PMID:17392385, PMID:24366376, PMID:26324357) and the case bundle for any validated functional/biochemical assay data on NM_032043.3:c.2593C>T (p.Arg865Trp) — e.g. helicase/ATPase activity, ICL repair complementation, foci formation, reversion assays. None of the cited full texts mention this specific variant or residue (865/R865W) despite PMID:31822495 being a BRIP1 missense functional-assay paper flagged 'functional' theme; its abstract describes cell-based functional assays for a panel of rare BRIP1 missense alleles but the variant identity within that panel could not be confirmed against this exact substitution in the retrieved text. No case-specific functional assay results are present in evidence.json/prefetch.json.
No applicable BRIP1 VCEP specification was retrieved; generic ACMG/AMP is therefore used. No case-control dataset in the evidence bundle reports an exact-variant carrier count for c.2593C>T (p.Arg865Trp) in affected individuals and controls, so enrichment cannot be assessed.
Generic ACMG/AMP PS4: increased prevalence in affected individuals compared with controls requires variant-specific enrichment evidence.
No affected individual with c.2593C>T reported together with a second pathogenic/likely pathogenic BRIP1 allele, and no phase evidence, is provided. PM3 cannot be applied.
Generic ACMG/AMP PM3: a variant must be observed in trans with a pathogenic variant in an affected individual for a recessive disorder.
No ClinGen VCEP/CSPEC exists for BRIP1, so generic ACMG PM5 was applied. The case's own PM5 candidate harvesting step explicitly declined to run a same-residue ClinVar search ('Unable to confirm classic same-residue PM5 semantics safely; skipping automatic candidate harvesting'), and no alternate missense change at codon 865 (e.g., p.Arg865Gln, p.Arg865Leu, p.Arg865Gly) with an established pathogenic/likely pathogenic classification appears anywhere else in the bundle.
Not assessed: there is no report that the exact variant was de novo in a proband with parental samples negative and parentage unconfirmed.
Generic ACMG/AMP 2015 de novo criterion (PM6); no BRIP1 VCEP/CSPEC was retrieved.
Not assessed: no evaluable family-level genotype/phenotype data or informative meioses are supplied. A ClinVar submission narrative reports that the variant did not co-segregate in one melanoma-affected family, so it cannot support PP1, but the underlying pedigree and genotypes are not available to quantify segregation.
Generic ACMG/AMP 2015 segregation criterion (PP1); no BRIP1 VCEP/CSPEC was retrieved.
No ClinGen VCEP/CSPEC exists for BRIP1, so generic ACMG PP2 was applied. Generic PP2 requires both (1) missense being a recognized mechanism of disease in the gene and (2) a low rate of benign missense variation in the gene. PMID:31822495 supports the first element -- it functionally characterizes multiple BRIP1 missense alleles (e.g., A349P, P47A, G690E, D791V) as hypomorphic or null and causally linked to Fanconi anemia / ICL-repair deficiency, establishing missense as a recognized BRIP1 disease mechanism. However, no missense constraint metric (e.g., gnomAD missense Z-score or observed/expected ratio) was located anywhere in the bundle to establish the second required element (rate of benign missense variation in this gene), and the same paper also notes 933-of-950 ClinVar BRIP1 missense variants are VUS, not benign, which does not itself establish a low benign-missense rate.
No applicable BRIP1 VCEP phenotype-specific specification was retrieved. The evidence bundle contains no proband phenotype, diagnostic workup, or phenotype-frequency data demonstrating that the presenting phenotype is highly specific for a BRIP1-related disorder.
Generic ACMG/AMP PP4: apply only when the patient's phenotype or family history is highly specific for a disease with a single genetic etiology.
The available population datasets establish rarity but do not provide phenotype- and age-ascertained observations of the exact variant in healthy adults sufficient for BS2. Zero homozygotes in gnomAD v2.1 and v4.1 does not supply BS2 evidence.
generic_acmg_amp: BS2 requires observation in healthy adults for a disorder expected to be fully penetrant at an early age
No gene-specific VCEP/CSPEC was found for BRIP1 (generic ACMG fallback). No functional assay evidence demonstrating normal/wild-type-like activity for NM_032043.3:c.2593C>T (p.Arg865Trp) was found in any cited full-text publication or in the case evidence files. PMID:31822495 describes a functional assay panel of BRIP1 missense alleles but this variant's presence and result in that panel could not be confirmed in the retrieved full text.
Not assessed: the reported lack of co-segregation in a single melanoma-affected family is insufficiently documented to establish strong non-segregation evidence. The bundle lacks the pedigree, relative-level genotypes and phenotypes, and an assessment of phenotype relevance and penetrance.
Generic ACMG/AMP 2015 non-segregation criterion (BS4); no BRIP1 VCEP/CSPEC was retrieved.
No observation places c.2593C>T in cis or trans with a pathogenic/likely pathogenic allele in a context that would support BP2. BP2 cannot be applied.
Generic ACMG/AMP BP2: the variant is observed in cis with a pathogenic variant, or in trans with a pathogenic variant for a fully penetrant dominant disorder.
No individual-level phenotype or molecular diagnostic result is provided to establish that the observed phenotype is fully explained by an alternative molecular diagnosis.
Generic ACMG/AMP BP5: apply when a variant is found in a case with an alternate molecular basis for disease.
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_032043.3:c.2593C>T in BRIP1 is a missense substitution predicted to produce NP_114432.2:p.(Arg865Trp). 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
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_032043.3:c.2593C>T in BRIP1 is a missense substitution predicted to produce NP_114432.2:p.(Arg865Trp). 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_032043.3:c.2593C>T in BRIP1 is a missense substitution predicted to produce NP_114432.2:p.(Arg865Trp). 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_032043.3:c.2593C>T in BRIP1 is a missense substitution predicted to produce NP_114432.2:p.(Arg865Trp). 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 BRIP1, mapped onto the exon structure of NM_032043.3. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| South Asian3 / 91,072 | 3.3e-05 |
| Remaining individuals2 / 62,502 | 3.2e-05 |
| European (non-Finnish)37 / 1,179,920 | 3.1e-05 |
| East Asian1 / 44,860 | 2.2e-05 |
| East Asian1 / 19,946 | 5e-05 |
| European (non-Finnish)6 / 128,716 | 4.7e-05 |
| South Asian1 / 30,608 | 3.3e-05 |
This variant is present in gnomAD v4.1 (AF= 2.66424e-05; MAF= 0.00266%, 43/1613968 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.2941e-05; MAF= 0.00329%, 3/91072 alleles, homozygotes = 0); grpmax FAF= 2.314e-05.
This variant is present in gnomAD v2.1 (AF= 2.83968e-05; MAF= 0.00284%, 8/281722 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.01354e-05; MAF= 0.00501%, 1/19946 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
Absent from gnomAD-Canada v1.0.
NM_032043.3:c.2593C>T (p.Arg865Trp) is a missense variant. No governing VCEP/CSPEC is available for BRIP1 (cspec.found=false; vcep_materials.final_classification_framework.found=false, framework falls back to generic ACMG/AMP 2015), and no gene-specific PP3/BP4 lookup spreadsheet was provided, so the generic calibrated in-silico approach applies. REVEL score = 0.804, which falls within the ClinGen SVI (Pejaver et al. 2022, PMID 36413997) calibrated 'Pathogenic Moderate' band (REVEL >= 0.773) for missense in-silico evidence, supporting PP3 at moderate strength. BayesDel score (0.398139) was also computed but is not used to support or contradict this call: no verified published calibration threshold/PMID for BayesDel is available to this pipeline, so per policy it is treated as not_available regardless of the raw score. SpliceAI predicts no meaningful splice disruption (max delta score = 0.066, well below any splice-altering threshold), so the splice-impact path is silent/non-contributory here (neither supports nor conflicts with the missense PP3 call) and is not itself sufficient to invoke PP3 via splicing. Align-GVGD/HCI prior data were not available for this variant (hci_prior.found=false).
REVEL >= 0.773 (ClinGen SVI Pejaver 2022 calibration, PMID 36413997) => PP3_Moderate for missense variant with no applicable VCEP override
The calibrated missense in-silico predictor (REVEL = 0.804) falls in the Pathogenic-Moderate range per ClinGen SVI calibration (PMID 36413997), i.e. in the pathogenic direction, not the benign direction, so BP4 cannot be applied for the missense path. SpliceAI shows no splice disruption (max delta = 0.066), which is simply an absence of a splicing signal for this missense variant rather than an independent benign in-silico protein-effect prediction, and is not sufficient on its own to invoke BP4 for a missense variant already showing a pathogenic-direction missense score. No VCEP-specific PP3/BP4 lookup override exists for BRIP1 to redirect this call.
REVEL >= 0.773 excludes BP4 under the missense in-silico path; SpliceAI absence-of-effect alone is insufficient for BP4 in a missense variant already carrying a pathogenic-direction predictor score
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_032043.3:c.2593C>T in BRIP1 is a missense substitution predicted to produce NP_114432.2:p.(Arg865Trp). 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 = 0.07). REVEL score = 0.804. BayesDel score = 0.398139.
7 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.
The majority of rare alleles (54-of-64) clustered within the highly conserved helicase domain (1-888 amino acids) and are predicted in silico to be deleterious to protein function... A subset of the missense variants identified fall within the seven highly conserved motifs of a DEAH helicase, but most lie outside of these domains.
Results section, paragraph on 'Increased number of BRIP1 missense allele carriers in ovarian and early onset breast cancer cohorts'
A variant observed to have arisen de novo (parental samples test negative), is considered strong support for pathogenicity if the following conditions are met: Both parental samples were shown through identity testing to be the biological parents of the patient. Note: PM6 applies if identity is assumed but not confirmed.
Section 'PS2 PM6 De novo variants'.
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= 2.66424e-05; MAF= 0.00266%, 43/1613968 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.2941e-05; MAF= 0.00329%, 3/91072 alleles, homozygotes = 0); grpmax FAF= 2.314e-05.
This variant is present in gnomAD v2.1 (AF= 2.83968e-05; MAF= 0.00284%, 8/281722 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.01354e-05; MAF= 0.00501%, 1/19946 alleles, homozygotes = 0); grpmax FAF= 5.239e-05.
Absent from gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Uncertain significance (15 clinical laboratories). (ClinVarID = 230320)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.804. BayesDel score = 0.398139.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV51997487, n = 5 times).
This variant does not lie in a statistically significant hotspot.