About NTRK1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
NTRK1 c.316G>A, p.(Val106Met)
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.
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Moderate
PM2 · moderate
This variant is present at extremely low frequency in population databases: gnomAD v2.1 AF=0.00080% (2/251,148 alleles), gnomAD v4.1 AF=0.00099% (16/1,613,972 alleles), both well below the 0.1% threshold for PM2. NTRK1-associated congenital insensitivity to pain with anhidrosis (CIPA) follows autosomal recessive inheritance, making PM2 applicable for variants at extremely low frequency in controls. No homozygotes have been observed.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.175 (below the 0.5 threshold, favoring benign), BayesDel score is -0.235671 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta score 0.05). All available in silico tools are concordant toward a benign interpretation.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 moderate, BP4 supporting benign; combination = 1 moderate + 1 supporting benign, 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
16 / 1,613,972 alleles
gnomAD v4.1: 16 / 1,613,972 alleles. Recorded AF 9.91343e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.96343e-06; MAF= 0.00080%, 2/251148 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26947e-05; MAF= 0.00327%, 1/30586 alleles, homozygotes = 0).
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.
ClinVar submissions
3 reported laboratory submissions
3 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. NTRK1, a receptor tyrosine kinase, is altered by gene fusions in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV100693989, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 21 not met · 1 not assessed · 2 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002529.3:c.316G>A (p.Val106Met) in NTRK1 was identified as a rare missense variant in exon 3 of the extracellular domain.
This variant is present at extremely low frequency in population databases: gnomAD v2.1 AF=0.00080% (2/251,148 alleles) and gnomAD v4.1 AF=0.00099% (16/1,613,972 alleles), with no homozygotes observed, meeting PM2 at moderate strength for an autosomal recessive disorder.
Multiple lines of computational evidence predict no deleterious effect: REVEL score is 0.175 (below the pathogenic threshold of 0.5), BayesDel is -0.235671 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta 0.05), meeting BP4 at supporting benign level.
This variant has been reported in ClinVar as Uncertain significance (ClinVar ID 655441) by three clinical laboratories (2-star review status). No expert panel has reviewed this variant, and no submitter has asserted a pathogenic or benign classification.
No variant-specific functional studies, segregation data, de novo reports, case-control data, or family studies were identified for NM_002529.3:c.316G>A. OncoKB reports 'Unknown Oncogenic Effect' with no reviewed variant-specific evidence. COSMIC reports one somatic occurrence (COSV100693989) without functional assay data.
Applying the generic ACMG/AMP 2015 final classification combination rules (PMID:25741868), the met criteria are PM2 (moderate pathogenic) and BP4 (supporting benign). These criteria are contradictory and do not satisfy any pathogenic or likely pathogenic combination, nor any benign or likely benign combination. The variant is classified as Uncertain significance (VUS).
No criteria match.
Met · 2
PM2 ModerateThis variant is present at extremely low frequency in population databases: gnomAD v2.1 AF=0.00080% (2/251,148 alleles), gnomAD v4.1 AF=0.00099% (16/1,613,972 alleles), both well below the 0.1% threshold for PM2. NTRK1-associated congenital insensitivity to pain with anhidrosis (CIPA) follows autosomal recessive inheritance, making PM2 applicable for variants at extremely low frequency in controls. No homozygotes have been observed. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 2/251
- 148 alleles (AF=7.96e-06
- 0.00080%)
- no homozygotes.
- gnomAD v4.1: 16/1
- 613
- 972 alleles (AF=9.91e-06
- 0.00099%)
- no homozygotes
- grpmax FAF=1.43e-05.
- gnomAD-Canada: absent.
- NTRK1 CIPA is autosomal recessive.
Still missing
- 16 alleles in gnomAD v4.1 may warrant scrutiny for potential undercalling or population substructure
- but AF remains below threshold.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.175 (below the 0.5 threshold, favoring benign), BayesDel score is -0.235671 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta score 0.05). All available in silico tools are concordant toward a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL: 0.175 (below 0.5 pathogenic threshold
- benign-leaning).
- BayesDel: -0.235671 (negative score
- predicts benign).
- SpliceAI: max delta 0.05 (no predicted splice impact).
Sources
Not met · 21 · evaluated, threshold not reached
PS1 No evidence that a different nucleotide change at codon 106 resulting in the same missense change (p.Val106Met) has been previously established as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar variation ID 655441 lists no alternative nucleotide changes at codon 106 producing V106M.
- PM5 candidates search found no same-residue comparator variants.
Still missing
- No systematic search for alternative nucleotide changes producing V106M was performed beyond ClinVar.
Sources
clinvar ↗pm5_candidates
PS2 No de novo data available for this variant. No publications or case submissions report a confirmed de novo occurrence of NM_002529.3:c.316G>A with confirmed parentage. Details ▾Hide ▴
Evidence considered
- ClinVar submissions do not report de novo origin for this variant.
- Literature_pass identified no de novo reports.
Still missing
- No parental testing data available.
Sources
PS3 No variant-specific functional studies have been performed on p.Val106Met. OncoKB reports 'Unknown Oncogenic Effect' with no reviewed functional evidence. No publications directly tested this variant or a systematically characterized range spanning codon 106 in a functional assay. Details ▾Hide ▴
Evidence considered
- OncoKB: 'Unknown Oncogenic Effect'
- no variant-specific functional data.
- Cancerhotspots: residue V106 is not in a statistically significant hotspot.
- COSMIC: 1 somatic occurrence (COSV100693989) but no functional assay data.
- Literature_pass identified no functional studies for this variant.
Still missing
- No in vitro or in vivo functional characterization of p.Val106Met.
- No systematic mutagenesis or tiling screen data spanning codon 106.
Sources
PS4 No case-control or cohort data demonstrate enrichment of this variant in affected individuals compared to controls. ClinVar shows 3 clinical laboratories classify this variant as VUS with no variant-specific case counts or prevalence data. Details ▾Hide ▴
Evidence considered
- ClinVar: 3 clinical laboratories report VUS
- no case enrichment data provided.
- PMID:20301726 flagged as candidate for PS4 in literature_pass but is a GeneReviews overview without variant-specific case enumeration.
Still missing
- No case-control study comparing frequency in CIPA patients vs. controls.
- No patient cohort data with this specific variant.
Sources
PM1 Residue Val106 does not lie in a statistically significant mutational hotspot per cancerhotspots.org, and no domain-specific functional evidence in the case materials establishes that the extracellular region spanning codon 106 is a critical functional domain where missense variants are established as pathogenic. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: residue V106 is not in a statistically significant hotspot.
- V106 is in the extracellular domain but no domain-specific functional characterization was provided in the case materials.
Still missing
- Domain-level functional annotation of the NTRK1 extracellular region was not specifically evaluated.
PM5 No different missense variant at the same residue (Val106) has been established as pathogenic. The PM5 candidates search found no comparator variants at codon 106 in ClinVar. Details ▾Hide ▴
Evidence considered
- PM5 candidates search returned 0 same-residue candidates.
- No expert-panel P/LP variant at codon 106 documented in the case materials.
Still missing
- Automated candidate harvesting was unable to confirm classic same-residue PM5 semantics.
Sources
pm5_candidates
PM6 No de novo data with or without confirmed paternity available for this variant. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar submissions or literature.
Still missing
- No parental testing data available.
Sources
PP1 No segregation data available for this variant. No family studies or cosegregation analyses have been reported. Details ▾Hide ▴
Evidence considered
- Literature_pass identified no segregation studies.
- ClinVar submissions do not include family-level segregation data.
Still missing
- No family studies with this variant available.
PP3 Multiple in silico predictors suggest a benign effect rather than a deleterious one. REVEL score is 0.175 (below the typical pathogenic threshold of 0.5), BayesDel score is -0.235671 (negative, favoring benign), and SpliceAI predicts no splicing impact (max delta 0.05). These scores are concordant with BP4, not PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.175 (benign-leaning
- below 0.5 threshold).
- BayesDel: -0.235671 (negative score
- favors benign).
- SpliceAI: max delta 0.05 (no predicted splice impact).
- HCI Prior: not available (gene not supported).
Sources
PP4 No patient phenotype or family history data specific to this variant were available in the case materials. The variant has been observed in clinical testing (ClinVar submissions for hereditary insensitivity to pain with anhidrosis and inborn genetic diseases), but no detailed phenotype descriptions were provided. Details ▾Hide ▴
Evidence considered
- ClinVar submissions list conditions 'Hereditary insensitivity to pain with anhidrosis' and 'Inborn genetic diseases' but provide no patient-specific phenotype details.
Still missing
- No detailed patient phenotype or family history available for review.
Sources
PP5 No reputable source has classified this variant as pathogenic. ClinVar consensus is Uncertain significance (2-star, criteria provided, multiple submitters, no conflicts). The GeneReviews article PMID:20301726 is a general NTRK1 CIPA overview; without full text, variant-specific mention cannot be confirmed. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance
- 2-star review status
- no P/LP assertion.
- PMID:20301726 (GeneReviews) is a gene-level overview
- no variant-specific classification confirmed.
Sources
BA1 Allele frequency is far below the BA1 threshold of 1%. The highest population frequency in gnomAD is 0.0044% (South Asian, v4.1) and the overall AF is 0.00099% (v4.1). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: overall AF=0.00080%
- max subpop AF=0.0033% (South Asian).
- gnomAD v4.1: overall AF=0.00099%
- max subpop AF=0.0044% (South Asian)
- grpmax FAF=1.43e-05.
- All frequencies well below BA1 threshold of 1%.
Sources
BS1 Allele frequency is below the BS1 threshold of 0.3%. The overall gnomAD v4.1 AF is 0.00099% and the highest subpopulation AF is 0.0044% (South Asian). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 overall AF=0.00099%
- max subpop AF=0.0044%.
- All frequencies below BS1 threshold of 0.3%.
Sources
BS2 No evidence that this variant has been observed in a healthy adult individual in trans with a known pathogenic variant in NTRK1. NTRK1-associated CIPA is autosomal recessive, so BS2 requires observation in trans with a pathogenic variant in an unaffected individual. Details ▾Hide ▴
Evidence considered
- No reports of this variant observed in trans with a pathogenic NTRK1 variant in a healthy adult.
Still missing
- No phase information or trans configuration data available.
BS3 No well-established in vitro or in vivo functional studies demonstrate that this variant has no deleterious effect. While in silico predictors (REVEL 0.175, BayesDel -0.235671) are concordant with a benign interpretation, these are computational, not experimental, and are addressed under BP4. Details ▾Hide ▴
Evidence considered
- No experimental functional assays (enzymatic activity
- protein expression
- signaling) performed on p.Val106Met.
- In silico scores are computational evidence
- not BS3-level experimental functional data.
Still missing
- No experimental functional characterization of p.Val106Met in receptor tyrosine kinase assays.
Sources
BS4 No segregation data available to evaluate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
- No family studies or cosegregation analyses available for this variant.
Still missing
- No segregation data available.
BP1 BP1 applies when a missense variant occurs in a gene where primarily truncating variants cause disease. NTRK1-associated CIPA is caused by both missense and truncating/loss-of-function variants. Multiple missense mutations across the NTRK1 gene are documented as pathogenic in CIPA patients. BP1 does not apply. Details ▾Hide ▴
Evidence considered
- NTRK1 CIPA is caused by both missense and truncating variants
- not a gene where only truncating variants cause disease.
- pvs1_gene_context confirms LOF mechanism but does not establish truncating-only pathogenesis.
Sources
pvs1_gene_context
BP2 No evidence of this variant observed in trans with a known pathogenic variant in NTRK1. Details ▾Hide ▴
Evidence considered
- No reports of trans configuration with a pathogenic NTRK1 variant.
Still missing
- No phase information or trans configuration data available.
BP5 No evidence that this variant has been observed in a case with an alternate molecular basis for disease. No co-occurring pathogenic variant data available. Details ▾Hide ▴
Evidence considered
- No reports of this variant co-occurring with a different pathogenic variant explaining the phenotype.
Still missing
- No data on co-occurring variants in affected individuals.
BP6 No reputable source has classified this variant as benign. ClinVar classification is Uncertain significance (2-star, 3 submitters), not Benign or Likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance
- 2 stars
- no benign or likely benign assertion.
Sources
PS5 No reputable source has classified this variant as pathogenic. ClinVar classification is Uncertain significance (2-star review status), and no expert panel or clinical laboratory has asserted a pathogenic or likely pathogenic classification. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (2 stars
- 3 submitters).
- No expert panel review or P/LP assertion from any source.
Sources
Not assessed · 1 · no assessment recorded
PP2 Insufficient data to evaluate. gnomAD constraint metrics (missense z-score, o/e ratio) for NTRK1 were not provided in the case materials, and no gene-level missense constraint analysis was included in the evidence brief. Cannot determine whether NTRK1 has a low rate of benign missense variation. Details ▾Hide ▴
Evidence considered
- No gnomAD gene constraint metrics (missense z-score
- o/e
- pLI) available for NTRK1 in the case materials.
Still missing
- Requires gnomAD gene constraint data for NTRK1 (missense z-score
- o/e ratio) to assess whether the gene tolerates benign missense variation.
Not applicable · 2· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_002529.3:c.316G>A is a missense substitution (NP_002520.2:p.Val106Met) and does not fall into any PVS1 null-variant category (nonsense, frameshift, canonical splice ±1/2, initiation codon, or exon deletion). Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution (V106M)
- not a null variant eligible for PVS1.
- pvs1_variant_assessment confirms bucket 'other' with apply_generic_pvs1_framework=false.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
BP7 N/ABP7 applies only to synonymous (silent) variants. NM_002529.3:c.316G>A is a missense variant (p.Val106Met), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Variant is missense (V106M)
- not synonymous.
Identifiers
- Gene
- NTRK1
- Transcript
- NM_002529.3
- Coding (HGVS c.)
- NM_002529.3:c.316G>A
- Protein (HGVS p.)
- NP_002520.2:p.(Val106Met)
- GRCh38
- chr1:156864756 G>A
- GRCh37
- chr1:156834548 G>A
- ClinVar
- 655441
- COSMIC
- COSV100693989
Gene diagram
Every interpreted variant in NTRK1, mapped onto the exon structure of NM_002529.3. Select a row to find it on the plot.
NTRK1NM_002529.3
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 NTRK1
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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
16 / 1,613,972 alleles
AF 9.91e-06 · 0 homozygotes · FAF 1.43e-05
gnomAD v2.1
2 / 251,148 alleles
AF 7.96e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 9.9e-06 · 16 / 1,613,972 alleles · 0 hom · FAF 1.4e-05
| South Asian4 / 91,058 | 4.4e-05 |
| Remaining individuals2 / 62,478 | 3.2e-05 |
| Admixed American1 / 59,996 | 1.7e-05 |
| African/African American1 / 74,900 | 1.3e-05 |
| European (non-Finnish)8 / 1,180,008 | 6.8e-06 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 8e-06 · 2 / 251,148 alleles · 0 hom
| South Asian1 / 30,586 | 3.3e-05 |
| Admixed American1 / 34,536 | 2.9e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 9.91343e-06; MAF= 0.00099%, 16/1613972 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 4.3928e-05; MAF= 0.00439%, 4/91058 alleles, homozygotes = 0); grpmax FAF= 1.426e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.96343e-06; MAF= 0.00080%, 2/251148 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26947e-05; MAF= 0.00327%, 1/30586 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.175
- BayesDel
- -0.236
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.175 (below the 0.5 threshold, favoring benign), BayesDel score is -0.235671 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta score 0.05). All available in silico tools are concordant toward a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL: 0.175 (below 0.5 pathogenic threshold
- benign-leaning).
- BayesDel: -0.235671 (negative score
- predicts benign).
- SpliceAI: max delta 0.05 (no predicted splice impact).
Sources
PP3 Multiple in silico predictors suggest a benign effect rather than a deleterious one. REVEL score is 0.175 (below the typical pathogenic threshold of 0.5), BayesDel score is -0.235671 (negative, favoring benign), and SpliceAI predicts no splicing impact (max delta 0.05). These scores are concordant with BP4, not PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.175 (benign-leaning
- below 0.5 threshold).
- BayesDel: -0.235671 (negative score
- favors benign).
- SpliceAI: max delta 0.05 (no predicted splice impact).
- HCI Prior: not available (gene not supported).
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants. NM_002529.3:c.316G>A is a missense variant (p.Val106Met), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Variant is missense (V106M)
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.175. BayesDel score = -0.235671.
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
-
PMID 23619275 ↗ACMG position statement on prenatal/preconception expanded carrier screening.ACMG position statement providing recommendations on prenatal/preconception expanded carrier screening. Discusses criteria for selecting disorders and mutations for population-based carrier screening panels. No mention of NTRK1 or any specific variant.Does not name this variant
-
PMID 20301726 ↗NTRK1 Congenital Insensitivity to Pain with Anhidrosis.Adam MP et al. · 1993GeneReviews clinical summary of NTRK1-associated congenital insensitivity to pain with anhidrosis (CIPA). Provides gene-level disease overview including inheritance, clinical characteristics, and general molecular genetics. Full text was not available in the case materials; abstract was not provided in publications.json.Does not name this variant
-
PMID 23037933 ↗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. · 2013Recommendations for including newborn screening bloodspot collection device serial numbers on birth certificates. Discusses newborn screening policy. No mention of NTRK1 or any specific genetic variant.Does not name this variant
-
PMID 24022298 ↗Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].European guidelines for offering prenatal diagnostic tests in clinical practice. Discusses general prenatal testing policy and clinical practice. No mention of NTRK1 or any specific genetic variant.Does not name this variant
-
PMID 31022120 ↗ACOG Committee Opinion No. 778 Summary: Newborn Screening and the Role of the Obstetrician-Gynecologist.ACOG Committee Opinion on newborn screening and the role of the obstetrician-gynecologist. Discusses newborn screening policy and clinical roles. No mention of NTRK1 or any specific genetic variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
16 / 1,613,972 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.050
Open source ↗
ClinVar
3 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/655441/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-156834548-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-156864756-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/1-156864756-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002529.3%3Ac.316G…
- OncoKB ↗www.oncokb.org/gene/NTRK1/V106M
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=184506365
- Cancer hotspots ↗www.cancerhotspots.org/
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= 9.91343e-06; MAF= 0.00099%, 16/1613972 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 4.3928e-05; MAF= 0.00439%, 4/91058 alleles, homozygotes = 0); grpmax FAF= 1.426e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.96343e-06; MAF= 0.00080%, 2/251148 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26947e-05; MAF= 0.00327%, 1/30586 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories). (ClinVarID = 655441)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.175. BayesDel score = -0.235671.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. NTRK1, a receptor tyrosine kinase, is altered by gene fusions in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV100693989, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.