CHEK2c.58C>TUncertain significance

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Variant interpretation report

CHEK2 c.58C>T, p.(Gln20Ter)

NM_007194.4:c.58C>T NP_009125.1:p.(Gln20Ter) View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

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

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About CHEK2

No gene-level summary was recorded for this case.

Key facts

Condition: CHEK2-related cancer predisposition
Inheritance: Autosomal dominant
Evidence used: 1 very strong (pathogenic) · 1 supporting (pathogenic)
Expert rules: ClinGen CHEK2 VCEP v1.0
Other laboratories (ClinVar): 15 Pathogenic · 3 Likely pathogenic · 1 Uncertain significance · 1 Likely Pathogenic · 1 pathogenic
Pipeline record: 26 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PVS1 (very strong): NM_007194.4:c.58C>T is a nonsense variant (p.Gln20Ter) in exon 2 of 15, resulting in premature termination at amino acid 20 of 544. This abolishes the entire protein product including the SQ/TQ-rich domain (residues 20-75), forkhead-associated domain (residues 115-165), and kinase domain (residues 225-490). NMD is predicted. CHEK2 loss of function is an established disease mechanism for CHEK2-related cancer predisposition (autosomal dominant). Under ClinGen SVI PVS1 recommendations (PMC6185798), a null variant in a gene where LoF is a known mechanism qualifies for PVS1 at very strong strength.
PM2 (supporting): This variant is present at very low frequency in population databases. gnomAD v4.1 reports an overall allele frequency of 0.0063% (102/1,613,966 alleles, 0 homozygotes). gnomAD v2.1 reports 0.014% (35/247,462 alleles, 0 homozygotes). The highest subpopulation frequency is in South Asian: 0.111% (gnomAD v4.1), still below 0.1% for the masking filter (grpmax FAF 0.093%). Overall frequency is well below the 0.1% threshold, supporting PM2 at supporting strength.

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

01The reasoning

How it was classified

The recorded framework is ClinGen CHEK2 VCEP v1.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

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

Pathogenic evidence criteria: 2 Benign evidence criteria: 0

Pathogenic criteria applied · 2

PVS1Very strong

PVS1 · very strong

NM_007194.4:c.58C>T is a nonsense variant (p.Gln20Ter) in exon 2 of 15, resulting in premature termination at amino acid 20 of 544. This abolishes the entire protein product including the SQ/TQ-rich domain (residues 20-75), forkhead-associated domain (residues 115-165), and kinase domain (residues 225-490). NMD is predicted. CHEK2 loss of function is an established disease mechanism for CHEK2-related cancer predisposition (autosomal dominant). Under ClinGen SVI PVS1 recommendations (PMC6185798), a null variant in a gene where LoF is a known mechanism qualifies for PVS1 at very strong strength.

PM2Supporting

PM2 · supporting

This variant is present at very low frequency in population databases. gnomAD v4.1 reports an overall allele frequency of 0.0063% (102/1,613,966 alleles, 0 homozygotes). gnomAD v2.1 reports 0.014% (35/247,462 alleles, 0 homozygotes). The highest subpopulation frequency is in South Asian: 0.111% (gnomAD v4.1), still below 0.1% for the masking filter (grpmax FAF 0.093%). Overall frequency is well below the 0.1% threshold, supporting PM2 at supporting strength.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CHEK2 Version 1.0 v1.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PVS1 very strong, PM2 supporting; combination = 1 very strong + 1 supporting, which maps to VUS.

02The sources

Evidence at a glance

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

gnomAD v4.1

gnomAD v2.1

Population frequency

102 / 1,613,966 alleles

gnomAD v4.1: 102 / 1,613,966 alleles. Recorded AF 6.31984e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000141436; MAF= 0.01414%, 35/247462 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00114589; MAF= 0.11459%, 35/30544 alleles, homozygotes = 0); grpmax FAF= 0.00084634.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.040 maximum delta

Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.

No listed criterion applied SpliceAI ↗

ClinVar submissions

21 reported laboratory submissions

15 Pathogenic · 3 Likely pathogenic · 1 Uncertain significance · 1 Likely Pathogenic · 1 pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

No matching record reported

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

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen CHEK2 VCEP v1.0, with the data and sources behind each one.

29 criteria with recorded statuses: 2 met · 18 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_007194.4:c.58C>T (p.Gln20Ter) is a nonsense variant in exon 2 of 15 of CHEK2, predicted to trigger NMD and abolish essentially the entire protein product including the SQ/TQ-rich, FHA, and kinase domains. CHEK2 loss of function is an established mechanism for autosomal dominant cancer predisposition.

This variant is observed at extremely low frequency in population databases: gnomAD v4.1 reports an overall allele frequency of 0.0063% (102/1,613,966 alleles, 0 homozygotes) and v2.1 reports 0.014% (35/247,462 alleles).

ClinVar classifies this variant as Pathogenic (ClinVarID 133887, 1-star review status), with 15 clinical laboratories reporting as Pathogenic and 3 as Likely Pathogenic.

One confirmed published case in a 48-year-old female with ER+/PR+/HER2+ invasive ductal breast carcinoma, identified among 7,657 Chinese BRCA1/2-negative breast cancer patients in Fan et al. (2018, PMID:29356917).

OncoKB classifies this variant as Likely Oncogenic and predicts Likely Loss-of-function based on the truncating nature of the variant.

Met · 2

PVS1 Very strongNM_007194.4:c.58C>T is a nonsense variant (p.Gln20Ter) in exon 2 of 15, resulting in premature termination at amino acid 20 of 544. This abolishes the entire protein product including the SQ/TQ-rich domain (residues 20-75), forkhead-associated domain (residues 115-165), and kinase domain (residues 225-490). NMD is predicted. CHEK2 loss of function is an established disease mechanism for CHEK2-related cancer predisposition (autosomal dominant). Under ClinGen SVI PVS1 recommendations (PMC6185798), a null variant in a gene where LoF is a known mechanism qualifies for PVS1 at very strong strength. Details ▾Hide ▴

Evidence considered

Nonsense variant at amino acid 20 of 544 (exon 2/15)
NMD predicted
truncation removes essentially the entire protein
CHEK2 LoF is established mechanism for autosomal dominant cancer predisposition
Consistent with CHEK2 CSPEC disease context (MONDO:0700271
CHEK2-related cancer predisposition)

Sources

pvs1_generic_framework ↗pvs1_gene_contextpvs1_variant_assessmentPMID:29356917 ↗

PM2 SupportingThis variant is present at very low frequency in population databases. gnomAD v4.1 reports an overall allele frequency of 0.0063% (102/1,613,966 alleles, 0 homozygotes). gnomAD v2.1 reports 0.014% (35/247,462 alleles, 0 homozygotes). The highest subpopulation frequency is in South Asian: 0.111% (gnomAD v4.1), still below 0.1% for the masking filter (grpmax FAF 0.093%). Overall frequency is well below the 0.1% threshold, supporting PM2 at supporting strength. Details ▾Hide ▴

Evidence considered

gnomAD v4.1: AF 0.0063% (102/1
613
966)
0 homozygotes
gnomAD v2.1: AF 0.014% (35/247
462)
grpmax FAF: 0.093% (v4.1) / 0.085% (v2.1)
Absent from most populations
concentrated in South Asian (SAS AF 0.111%)

Sources

gnomad_v2 ↗gnomad_v4 ↗

Not met · 18 · evaluated, threshold not reached

PS1 No same-amino-acid pathogenic missense change at codon 20 has been identified. The variant creates a premature stop codon; no comparator missense variants were identified that would satisfy PS1. Details ▾Hide ▴

No further detail was recorded.

PS2 No de novo occurrence data are available for this variant in any publication or database. Details ▾Hide ▴

Still missing

No de novo studies identified

PS3 No experimental functional data exist for NM_007194.4:c.58C>T (p.Gln20Ter) or for a systematically characterized range that includes position 20. OncoKB's Likely Oncogenic classification is derived from the truncating nature of the variant (loss-of-function), not from direct functional assay of this variant. Details ▾Hide ▴

Evidence considered

OncoKB labels variant as Likely Oncogenic / Likely Loss-of-function
but this inference is based on variant type (nonsense)
not experimental data

Still missing

No functional studies of c.58C>T or systematic functional characterization of the SQ/TQ domain

Sources

oncokb ↗

PS4 Only one confirmed observation of this variant in a published breast cancer patient (PMID:29356917, Fan et al. 2018: 1/7657 Chinese BRCA1/2-negative breast cancer patients). The original report by Baloch et al. (PMID:27039729/27510020) is cited but full text is unavailable to confirm case count. Insufficient case-control data to establish significantly increased prevalence in affected individuals. Details ▾Hide ▴

Evidence considered

1 confirmed observation in 7657 BRCA1/2-negative breast cancer patients (Fan et al. 2018)
Original report Baloch et al. 2016 cited but full text unavailable for case count verification
ClinVar: 15 clinical labs classify as Pathogenic
suggesting additional clinical observations but not a published case-control cohort

Still missing

Full text of Baloch et al. (PMID:27039729) unavailable
published case-control data lacking

Sources

PMID:29356917 ↗clinvar ↗

PM1 The variant falls at codon 20, the first residue of the SQ/TQ-rich domain (residues 20-75). While this is a functionally characterized regulatory domain in CHEK2, the evidence that this domain is critical is already fully captured by PVS1 (very_strong). Applying PM1 in addition would constitute double-counting of the same domain-loss evidence. The variant position is not in a statistically significant cancerhotspots.org hotspot. Details ▾Hide ▴

Evidence considered

Position 20 is within the SQ/TQ-rich domain (residues 20-75)
a characterized CHEK2 regulatory domain
Not in a statistically significant cancer hotspot
Domain-level evidence already accounted for by PVS1

Sources

PMID:29356917 ↗

PM5 The variant creates a premature stop codon (p.Gln20Ter). PM5 requires a different pathogenic missense change at the same amino acid residue. No pathogenic missense variant at codon 20 has been identified in ClinVar. The automated PM5 candidate search found no eligible comparator variants. Details ▾Hide ▴

Evidence considered

No same-residue pathogenic missense comparators identified
Variant is nonsense (Gln→Ter)
not amenable to classic PM5 comparison

Sources

pm5_candidates

PM6 No de novo occurrence data are available for this variant in any publication or database. Details ▾Hide ▴

Still missing

No de novo studies identified

PP1 No co-segregation data available. The single confirmed published case (PMID:29356917, Case 9193, 48-year-old female) had no reported family history of breast/ovarian cancer, precluding co-segregation analysis. Details ▾Hide ▴

Evidence considered

Single published case (Fan et al. 2018) had no family history of breast/ovarian cancer

Still missing

No multi-generational pedigrees with segregation data available

Sources

PMID:29356917 ↗

PP4 The single confirmed published case (PMID:29356917, Case 9193: 48F, ER+/PR+/HER2+ IDC, grade II) had no family history of breast/ovarian cancer. While the broader CHEK2 mutation cohort in Fan et al. showed enrichment for PR-positive (88.5% vs 64.5%, p=0.011) and lymph node-positive disease (53.8% vs 27.3%, p=0.002), these features are not sufficiently specific to this individual variant to meet PP4. Insufficient phenotype specificity for a single case to apply PP4. Details ▾Hide ▴

Evidence considered

CHEK2 mutation carriers show enrichment for PR+ and LN+ breast cancer (Fan et al. 2018)
Single Q20X case had ER+/PR+/HER2+ IDC
grade II
LN+
no family history

Still missing

Larger case series of Q20X-specific phenotype not available

Sources

PMID:29356917 ↗

PP5 ClinVar classifies this variant as Pathogenic (ClinVarID 133887) with review status 'criteria provided, single submitter' (1-star). Under current rules, PP5 at supporting strength requires ClinVar 3-star expert panel review. Despite strong clinical laboratory consensus (15 labs Pathogenic, 3 Likely Pathogenic, 1 VUS), the 1-star review status does not meet the 3-star threshold for PP5 application. Details ▾Hide ▴

Evidence considered

ClinVarID 133887: Pathogenic
1-star (criteria provided
single submitter)
15 clinical labs classify as Pathogenic
3 as Likely Pathogenic
Review status does not meet 3-star EP threshold for PP5

Still missing

No ClinGen expert panel review for this variant

Sources

clinvar ↗

BA1 Overall allele frequency in gnomAD v4.1 is 0.0063%, far below the BA1 threshold of 1%. The highest subpopulation frequency (South Asian) is 0.111%, also well below 1%. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 AF: 0.0063% (overall)
0.111% (SAS max)
Both well below BA1 threshold of 1%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 Overall allele frequency in gnomAD v4.1 is 0.0063%, below the BS1 threshold of 0.3%. The highest subpopulation frequency (South Asian) is 0.111%, also below 0.3%. This variant is too rare in population databases to meet BS1. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 AF: 0.0063% (overall)
0.111% (SAS max)
Both well below BS1 threshold of 0.3%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No homozygous individuals identified in gnomAD (v2.1 or v4.1). No evidence that this variant has been observed in trans with a pathogenic CHEK2 variant or that healthy homozygous carriers exist. Insufficient data to apply BS2. Details ▾Hide ▴

Evidence considered

0 homozygotes in gnomAD v2.1 (247
462 alleles) and v4.1 (1
613
966 alleles)

Still missing

No observation of homozygous state or in-trans occurrence

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No functional studies demonstrating that this variant does not impair protein function. On the contrary, the nonsense change at codon 20 is predicted to produce a severely truncated, non-functional protein via NMD. Details ▾Hide ▴

Still missing

No functional studies available

BS4 No segregation data demonstrating lack of co-segregation with disease. The single published case had no family history for co-segregation analysis. Details ▾Hide ▴

Still missing

No segregation data available

BP2 No evidence that this variant has been observed in trans with a known pathogenic CHEK2 variant. Details ▾Hide ▴

Still missing

No in-trans observations available

BP5 No evidence that this variant has been observed in a case with an alternative molecular basis for disease. Details ▾Hide ▴

Still missing

No cases with alternative molecular diagnosis identified

BP6 ClinVar classifies this variant as Pathogenic, not benign. No reputable source reports this variant as benign. BP6 is not applicable. Details ▾Hide ▴

Evidence considered

ClinVar classification: Pathogenic (not benign)

Sources

clinvar ↗

Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴

PM3 N/ASkipped — recessive disorder criterion, not applicable for autosomal dominant CHEK2-related cancer predisposition. Details ▾Hide ▴

No further detail was recorded.

PM4 N/ASkipped — protein length change criterion (in-frame deletion/insertion), not applicable to substitution variants. Details ▾Hide ▴

No further detail was recorded.

PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation. This is a nonsense (truncating) variant, not a missense variant. Details ▾Hide ▴

No further detail was recorded.

PP3 N/AIn silico prediction tools (REVEL, BayesDel, SpliceAI) are designed to assess the impact of missense variants and splice alterations. For a nonsense variant (p.Gln20Ter) where the primary mechanism is NMD/truncation, these tools are not informative. SpliceAI confirms no splice alteration (max delta 0.04). Details ▾Hide ▴

Evidence considered

SpliceAI max delta 0.04 — no predicted splice impact
BayesDel score 0.567 not informative for nonsense variant

Sources

spliceai ↗bayesdel

BP1 N/ABP1 applies to missense variants in genes where only truncating variants cause disease. This variant IS a truncating (nonsense) variant, so BP1 is not applicable. Details ▾Hide ▴

No further detail was recorded.

BP3 N/ASkipped — in-frame deletion/insertion criterion, not applicable to substitution variants. Details ▾Hide ▴

No further detail was recorded.

BP4 N/ABP4 relies on in silico predictions (REVEL, BayesDel, etc.) that multiple algorithms predict no impact. These tools evaluate amino acid substitution effects and are not informative for nonsense variants where the primary mechanism is NMD/truncation. SpliceAI shows no splice impact (max delta 0.04), but BP4 for a nonsense variant is not applicable. Details ▾Hide ▴

Evidence considered

SpliceAI max delta 0.04 — no predicted splice alteration

Sources

spliceai ↗

BP7 N/ABP7 applies to synonymous variants where splicing algorithms predict no impact. This is a nonsense (stop-gain) variant, not a synonymous variant. Details ▾Hide ▴

No further detail was recorded.

PS5 N/APS5 applies to recessive disorders; CHEK2-related cancer predisposition is autosomal dominant. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: CHEK2
Transcript: NM_007194.4
Coding (HGVS c.): NM_007194.4:c.58C>T
Protein (HGVS p.): NP_009125.1:p.(Gln20Ter)
GRCh38: chr22:28734664 G>A
GRCh37: chr22:29130652 G>A
ClinVar: 133887

Gene diagram

Every interpreted variant in CHEK2, mapped onto the exon structure of NM_007194.4. Select a row to find it on the plot.

CHEK2NM_007194.4

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 CHEK2 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 102 / 1,613,966 alleles AF 6.32e-05 · 0 homozygotes · FAF 0.000933

gnomAD v2.1 35 / 247,462 alleles AF 0.000141 · 0 homozygotes · FAF 0.000846

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.3e-05 · 102 / 1,613,966 alleles · 0 hom · FAF 0.00093

South Asian101 / 91,068	0.0011
Middle Eastern1 / 6,062	0.00016

0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).

gnomAD v2.1

AF 0.00014 · 35 / 247,462 alleles · 0 hom · FAF 0.00085

South Asian35 / 30,544

0.0011

0 alternate alleles recorded in 7 other groups: African/African American, Admixed 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= 6.31984e-05; MAF= 0.00632%, 102/1613966 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00110906; MAF= 0.11091%, 101/91068 alleles, homozygotes = 0); grpmax FAF= 0.00093302.

gnomAD v2.1

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +63 bp

0.040

SpliceAI acceptor gainat -171 bp

0.020

SpliceAI donor lossat -261 bp

0.010

SpliceAI donor gainat +63 bp

0.000

Pangolin splice lossmagnitude shown

-0.100

Pangolin splice gain

0.020

Other predictors

REVEL: Not available
BayesDel: 0.567

How the predictions were used

Evidence considered

SpliceAI max delta 0.04 — no predicted splice impact
BayesDel score 0.567 not informative for nonsense variant

Sources

spliceai ↗bayesdel

Evidence considered

SpliceAI max delta 0.04 — no predicted splice alteration

Sources

spliceai ↗

BP7 N/ABP7 applies to synonymous variants where splicing algorithms predict no impact. This is a nonsense (stop-gain) variant, not a synonymous variant. Details ▾Hide ▴

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). BayesDel score = 0.566539.

7 paper records listed. 1 cited in the classification.

Cited in the classification

Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2-negative breast cancer patients.

Fan Z et al. · 2018 May

Fan et al. (2018) screened CHEK2 in 7,657 Chinese BRCA1/2-negative breast cancer patients and identified c.C58T (p.Q20X) in one patient (0.013%). The carrier was a 48-year-old female with ER+/PR+/HER2+ invasive ductal carcinoma, grade II, lymph node-positive, no family history of breast/ovarian cancer. The variant maps to the SQ/TQ-rich domain and is referenced to Baloch et al. as the original report.
→ PVS1 Names this variant
PMID 29356917 ↗
Source detail

c.C58T p.Q20X SQ/TQ 1 Baloch et al. [43].

Location Table 1 (mutation list), Table 3 (Case 9193 clinical details), Results para 3, Discussion

Other recorded publications

Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

Decker B et al. · 2017

Decker et al. (2017) sequenced ATM, CHEK2, PALB2, and XRCC2 coding regions in 13,087 breast cancer cases and 5,488 controls. This study analyzed CHEK2 protein-truncating variants aggregated as a class rather than specific variants. NM_007194.4:c.58C>T was not individually identified in this paper.
Does not name this variant
PMID 28779002 ↗
Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband.

Cybulski et al. (2009) studied cancer risks in first-degree relatives of CHEK2 mutation carriers, focusing on common Polish founder mutations (1100delC, IVS2+1G>A, I157T, del5395). NM_007194.4:c.58C>T was not among the variants analyzed.
Does not name this variant
PMID 19401704 ↗
Incorporating truncating variants in PALB2, CHEK2, and ATM into the BOADICEA breast cancer risk model.

Lee et al. (2016) extended the BOADICEA breast cancer risk model to incorporate truncating variants in PALB2, CHEK2, and ATM. The model handles truncating variants as a class; NM_007194.4:c.58C>T is not individually mentioned.
Does not name this variant
PMID 27464310 ↗
Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

Foley SB et al. · 2015

Foley et al. (2015) performed whole-genome sequencing on 258 cancer genetics patients (BRCA1/2-positive and negative). The study focused on diagnostic yield of WGS. NM_007194.4:c.58C>T was not individually identified.
Does not name this variant
PMID 26023681 ↗
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.

Capalbo A et al. · 2019

Capalbo et al. (2019) analyzed exome sequencing data from 14,125 individuals undergoing preconception carrier screening. NM_007194.4:c.58C>T was not individually identified in this paper.
Does not name this variant
PMID 31589614 ↗
Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

This is a National Society of Genetic Counselors practice guideline for cancer genetic risk assessment and counseling. It does not discuss specific variants. NM_007194.4:c.58C>T is not mentioned.
Does not name this variant
PMID 15604628 ↗

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

gnomAD v4.1 102 / 1,613,966 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.040 Open source ↗

ClinVar 15 Pathogenic · 3 Likely pathogenic · 1 Uncertain significance · 1 Likely Pathogenic · 1 pathogenic 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 ↗

ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

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

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (15 clinical laboratories) and as Likely pathogenic (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Likely Pathogenic (1 clinical laboratory) and as pathogenic (1 clinical laboratory). (ClinVarID = 133887)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). BayesDel score = 0.566539.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Somatic

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

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.