0%
CDK12c.2964C>TLikely benign
Print report
Variant interpretation report

CDK12 c.2964C>T, p.(Phe988=)

NM_016507.4:c.2964C>T NP_057591.2:p.(Phe988=) View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

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

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About CDK12

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

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

Pathogenic evidence criteria: 0 Benign evidence criteria: 3
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3
BS1Strong
BS1 · strong

The allele frequency of NM_016507.4:c.2964C>T in population databases exceeds the threshold expected for a pathogenic CDK12 variant. In gnomAD v2.1, the variant has a grpmax filtering allele frequency of 0.798% (African/African American subpopulation AF 0.885%) with 2 homozygous individuals. In gnomAD v4.1, the grpmax FAF is 0.781% (African/African American AF 0.835%) with 4 homozygous individuals. These frequencies are well above the BS1 threshold of >0.3% for a rare Mendelian disorder gene, supporting that this variant is too common in the general population to be pathogenic.

BP4Supporting
BP4 · supporting

Computational evidence predicts no impact on splicing for this synonymous variant. SpliceAI assigns a maximum delta score of 0.02 (well below the 0.2 threshold), with no predicted donor gain, donor loss, acceptor gain, or acceptor loss. This supports a benign interpretation.

BP7Supporting
BP7 · supporting

NM_016507.4:c.2964C>T is a synonymous variant (p.Phe988=) with SpliceAI predicting no splice impact (max delta score 0.02). No donor/acceptor gain or loss is predicted. The nucleotide substitution is not at a highly conserved splice consensus position and computational predictions support no effect on splicing. BP7 is met at supporting benign strength.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong benign, BP4 supporting benign, BP7 supporting benign; combination = 1 strong benign + 2 supporting benign, which maps to Likely Benign.

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
715 / 1,613,708 alleles

gnomAD v4.1: 715 / 1,613,708 alleles. Recorded AF 0.000443079. Recorded homozygote count 4.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000859641; MAF= 0.08596%, 243/282676 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00885133; MAF= 0.88513%, 221/24968 alleles, homozygotes = 2); grpmax FAF= 0.00797854.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0008686210640608035, 16/18420 alleles, homozygotes = 0).

Applied · BS1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.020 maximum delta

Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions

2 Likely benign · 1 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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 Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 3 met · 18 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_016507.4:c.2964C>T (p.Phe988=) is a synonymous variant in CDK12. This variant is present in gnomAD at a grpmax filtering allele frequency of 0.798% (v2.1) and 0.781% (v4.1), with an African/African American subpopulation frequency of 0.885%, meeting BS1 at strong benign strength.

The variant is observed in 2 homozygous individuals in gnomAD v2.1 and 4 homozygous individuals in gnomAD v4.1, further supporting that biallelic presence is tolerated in the general population.

SpliceAI predicts no impact on splicing (max delta score 0.02), consistent with a synonymous variant that does not alter the protein product or disrupt normal mRNA processing, meeting BP7 at supporting benign strength.

Computational splicing predictions show no evidence of splice site disruption, meeting BP4 at supporting benign strength.

ClinVar reports this variant as Likely benign (2 clinical laboratories) and Benign (1 clinical laboratory); however the review status is 1-star (criteria provided, single submitter) and does not independently meet the 3-star expert panel threshold for BP6.

No pathogenic criteria are met. BS1 (strong benign), BP4 (supporting benign), and BP7 (supporting benign) together support a classification of Likely benign per ACMG/AMP 2015 guidelines.

Met · 3

BS1 StrongThe allele frequency of NM_016507.4:c.2964C>T in population databases exceeds the threshold expected for a pathogenic CDK12 variant. In gnomAD v2.1, the variant has a grpmax filtering allele frequency of 0.798% (African/African American subpopulation AF 0.885%) with 2 homozygous individuals. In gnomAD v4.1, the grpmax FAF is 0.781% (African/African American AF 0.835%) with 4 homozygous individuals. These frequencies are well above the BS1 threshold of >0.3% for a rare Mendelian disorder gene, supporting that this variant is too common in the general population to be pathogenic. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: total AF 0.086% (243/282
  • 676 alleles)
  • African/African American AF 0.885% (221/24
  • 968 alleles)
  • grpmax FAF 0.798%
  • 2 homozygotes.
  • gnomAD v4.1: total AF 0.044% (715/1
  • 613
  • 708 alleles)
  • African/African American AF 0.835% (626/74
  • 982 alleles)
  • grpmax FAF 0.781%
  • 4 homozygotes.
  • Both grpmax FAF values and African subpopulation AF significantly exceed the BS1 threshold of >0.3%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingComputational evidence predicts no impact on splicing for this synonymous variant. SpliceAI assigns a maximum delta score of 0.02 (well below the 0.2 threshold), with no predicted donor gain, donor loss, acceptor gain, or acceptor loss. This supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.02: no donor/acceptor gain or loss
  • no significant splicing impact predicted.
Still missing
  • REVEL and BayesDel scores unavailable for this synonymous variant
  • limiting to splicing prediction only.
Sources
spliceai ↗
BP7 SupportingNM_016507.4:c.2964C>T is a synonymous variant (p.Phe988=) with SpliceAI predicting no splice impact (max delta score 0.02). No donor/acceptor gain or loss is predicted. The nucleotide substitution is not at a highly conserved splice consensus position and computational predictions support no effect on splicing. BP7 is met at supporting benign strength. Details ▾Hide ▴
Evidence considered
  • Synonymous variant producing p.(Phe988=).
  • SpliceAI max delta score 0.02: no donor or acceptor site gain or loss predicted.
  • Nucleotide substitution is not within the splice consensus region.
Sources
spliceai ↗

Not met · 18 · evaluated, threshold not reached

PS1 PS1 requires a different nucleotide change at the same codon producing the same missense change that has been previously classified as pathogenic. This is a synonymous variant (p.Phe988=) and does not produce a missense change. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • no missense amino acid change to compare against an established pathogenic variant at this codon.
PS2 No evidence of de novo occurrence for NM_016507.4:c.2964C>T in any published study or database. No parent-of-origin testing data available. Details ▾Hide ▴
Evidence considered
  • No de novo reports identified in ClinVar submissions
  • literature
  • or databases for this variant.
Still missing
  • No parental testing data available.
PS3 No functional data identified for this synonymous variant. OncoKB lists this variant as 'Unknown Oncogenic Effect' with no associated curated publications. No experimental studies testing NM_016507.4:c.2964C>T were found in the literature. Details ▾Hide ▴
Evidence considered
  • OncoKB classification: Unknown Oncogenic Effect
  • no variant-specific functional publications curated.
  • Synonymous variant with no predicted protein alteration
  • functional studies of this exact variant are absent from the literature.
Still missing
  • No functional assays performed on this synonymous variant.
Sources
oncokb ↗
PS4 No case-control studies demonstrating enrichment of this variant in affected individuals compared to controls. The literature papers associated with this variant via ClinVar are BRCA-focused clinical guidelines (PMID:17392385, 23188549, 24366376, 24366402, 24493721) and a population survey (PMID:24728327) that do not mention CDK12 or this variant. No variant-specific case observations were identified. Details ▾Hide ▴
Evidence considered
  • No case-control data or cohort studies reporting enrichment of c.2964C>T in CDK12-associated disease.
  • The variant is present at appreciable frequency in gnomAD population controls (total AF 0.086%
  • African AF 0.885%)
  • inconsistent with a rare pathogenic variant.
Still missing
  • No disease-specific cohort data for this variant.
PM1 Although CDK12 contains a kinase domain (approximately residues 723-1002) and position 988 falls within the C-terminal region of this domain, this is a synonymous variant (p.Phe988=) with no predicted splice impact (SpliceAI max delta 0.02). The variant does not alter the protein product or disrupt a functional domain. Cancerhotspots.org does not list this residue as a statistically significant hotspot. PM1 requires a variant that alters or disrupts a critical functional domain, which is not the case for a synonymous substitution with no splicing consequences. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.02: no predicted splice impact.
  • Cancerhotspots.org: residue not statistically significant.
  • Synonymous variant does not alter the CDK12 kinase domain or protein product.
Sources
spliceai ↗
PM2 This variant is present in gnomAD population databases at a frequency exceeding the PM2 threshold of <0.1%. In gnomAD v2.1 the variant has a total allele frequency of 0.086% (243/282,676 alleles) and a maximum subpopulation frequency of 0.885% in the African/African American population (221/24,968 alleles, 2 homozygotes); grpmax FAF is 0.798%. In gnomAD v4.1 the variant has 715/1,613,708 alleles (0.044%) with African/African American AF of 0.835% (626/74,982 alleles, 4 homozygotes); grpmax FAF is 0.781%. The grpmax filtering allele frequency in both datasets is well above 0.1%, so PM2 is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: 243/282
  • 676 alleles (0.086%)
  • grpmax FAF 0.798%
  • African AF 0.885%
  • 2 homozygotes.
  • gnomAD v4.1: 715/1
  • 613
  • 708 alleles (0.044%)
  • grpmax FAF 0.781%
  • African AF 0.835%
  • 4 homozygotes.
  • Both grpmax FAF values exceed the PM2 threshold of <0.1%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
PM6 No evidence of de novo occurrence for NM_016507.4:c.2964C>T. No published reports or database entries document this variant arising de novo with confirmed maternity and paternity. Details ▾Hide ▴
Evidence considered
  • No de novo reports identified for this variant.
Still missing
  • No parental testing data available.
PP1 No cosegregation data available for NM_016507.4:c.2964C>T with disease in affected family members. Details ▾Hide ▴
Evidence considered
  • No family studies or segregation analyses identified for this variant.
Still missing
  • No segregation data available.
PP3 In silico prediction tools do not support a deleterious effect. REVEL and BayesDel scores are not available for this variant. SpliceAI predicts no splice impact (max delta score 0.02, well below the 0.2 threshold). No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.02: no donor/acceptor gain or loss
  • no splicing impact predicted.
  • REVEL and BayesDel scores unavailable for this synonymous variant.
Still missing
  • REVEL and BayesDel scores not computable for this synonymous variant.
Sources
spliceai ↗
PP4 No evidence that the patient's phenotype or family history is highly specific for CDK12-related disease. PP4 requires a phenotype highly specific for a disease with a single genetic etiology. Details ▾Hide ▴
Evidence considered
  • No phenotype specificity data available for this case.
Still missing
  • Patient phenotype information not provided for specificity assessment.
PP5 ClinVar lists this variant as 'Likely benign' (ClinVar Variation ID 133856) with review status 'criteria provided, single submitter' (1-star). PP5 requires a reputable source (i.e., expert panel with 3-star review status) to have classified the variant as pathogenic. The current review status does not meet the threshold for PP5 application. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 133856: Likely benign
  • criteria provided
  • single submitter (1-star review status). Not an expert panel (3-star) classification.
Sources
clinvar ↗
BA1 The maximum subpopulation allele frequency in gnomAD is 0.885% in the African/African American population (gnomAD v2.1), with a grpmax FAF of 0.798%. These are below the BA1 threshold of >1.0%. The variant is not common enough to be considered a benign population polymorphism under BA1. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 African/African American AF: 0.885% (221/24
  • 968 alleles).
  • gnomAD v2.1 grpmax FAF: 0.798%.
  • gnomAD v4.1 African/African American AF: 0.835% (626/74
  • 982 alleles).
  • All frequency values below BA1 threshold of >1.0%.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 Although the variant is observed in 2 homozygous individuals in gnomAD v2.1 and 4 homozygous individuals in gnomAD v4.1, BS2 requires observation in a healthy adult for a disorder with full penetrance expected at an early age. CDK12 germline variants are associated with adult-onset prostate cancer susceptibility, which is not a fully penetrant early-onset disorder. Under strict ACMG/AMP criteria, the homozygous observations do not satisfy BS2 for a late-onset, incompletely penetrant condition. Details ▾Hide ▴
Evidence considered
  • 2 homozygous individuals in gnomAD v2.1
  • 4 homozygous individuals in gnomAD v4.1.
  • CDK12 germline disease is adult-onset prostate cancer
  • not a fully penetrant early-onset disorder required for strict BS2 application.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No functional studies demonstrating a neutral (benign) effect for NM_016507.4:c.2964C>T. BS3 requires well-established in vitro or in vivo functional studies showing no damaging effect on protein function or splicing. No such studies have been conducted for this synonymous variant. Details ▾Hide ▴
Evidence considered
  • No functional assays performed on this variant to demonstrate neutral effect.
Still missing
  • No functional data available for this variant.
BS4 No cosegregation data available demonstrating lack of segregation with disease for NM_016507.4:c.2964C>T. BS4 requires observation of the variant in multiple family members who do not have the disease (non-segregation with disease). Details ▾Hide ▴
Evidence considered
  • No family studies or non-segregation data available for this variant.
Still missing
  • No segregation or non-segregation data available.
BP2 No evidence of this variant observed in trans with a known pathogenic variant in CDK12. BP2 requires observation in trans with a pathogenic variant for a dominantly inherited disorder, or in cis with a pathogenic variant in a recessive disorder. Details ▾Hide ▴
Evidence considered
  • No phase data or co-occurrence data with another CDK12 pathogenic variant available.
Still missing
  • No phase information available.
BP5 No evidence that this variant is found in a case with an alternate molecular basis for disease. No patient-level data available to assess whether an alternate genetic cause explains the phenotype. Details ▾Hide ▴
Evidence considered
  • No alternate molecular basis identified in any case harboring this variant.
Still missing
  • No patient-level phenotype or genotype data to evaluate alternate molecular basis.
BP6 ClinVar reports this variant as 'Likely benign' (Variation ID 133856) with review status 'criteria provided, single submitter' (1-star). BP6 requires a reputable source (3-star expert panel review) to have classified the variant as benign. The current 1-star review status does not meet the threshold for BP6 application. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 133856: Likely benign (2 submitters) and Benign (1 submitter)
  • review status 'criteria provided
  • single submitter' (1-star). Not an expert panel classification.
Sources
clinvar ↗
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_016507.4:c.2964C>T is a synonymous variant (p.Phe988=) with no predicted impact on splicing (SpliceAI max delta 0.02). PVS1 requires a null variant (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, or exon deletion) and does not apply to synonymous substitutions outside the splice consensus. Details ▾Hide ▴
Evidence considered
  • Synonymous variant p.(Phe988=) with SpliceAI max delta score 0.02
  • no splice impact predicted.
  • PVS1 variant assessment classifies this variant as bucket 'other'
  • explicitly not eligible for generic PVS1 framework.
Sources
spliceai ↗pvs1_variant_assessmentpvs1_gene_context
PM5 N/APM5 requires an alternate missense change at the same codon that has been classified as pathogenic. This variant is synonymous (p.Phe988=) and does not produce a missense change, so no comparator missense variant at codon 988 can be evaluated under PM5. Details ▾Hide ▴
Evidence considered
  • PM5 candidates artifact confirms: variant is synonymous
  • cannot establish classic same-residue PM5 semantics.
Sources
pm5_candidates
PP2 N/APP2 specifically applies to missense variants in genes with a low rate of benign missense variation where missense variants are a common disease mechanism. This is a synonymous variant (p.Phe988=) and does not meet the missense requirement for PP2. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • PP2 is defined for missense variants only.
BP1 N/ABP1 applies to missense variants in a gene where truncating variants are a known mechanism of disease. This is a synonymous variant (p.Phe988=) and does not meet the missense requirement for BP1. Details ▾Hide ▴
Evidence considered
  • Synonymous variant
  • BP1 is defined for missense variants only.
PS5 N/APS5 requires a different pathogenic missense variant at the same codon. This is a synonymous variant that does not alter the amino acid; the PS5 framework for same-codon comparator variants does not apply. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene
CDK12
Transcript
NM_016507.4
Coding (HGVS c.)
NM_016507.4:c.2964C>T
Protein (HGVS p.)
NP_057591.2:p.(Phe988=)
GRCh38
chr17:39519956 C>T
GRCh37
chr17:37676209 C>T
ClinVar
133856

Gene diagram

Every interpreted variant in CDK12, mapped onto the exon structure of NM_016507.4. Select a row to find it on the plot.

CDK12NM_016507.4
Fetching transcript structure from UCSC…
gnomAD v4.1 715 / 1,613,708 alleles AF 0.000443 · 4 homozygotes · FAF 0.00781
gnomAD v2.1 243 / 282,676 alleles AF 0.00086 · 2 homozygotes · FAF 0.00798
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.00044 · 715 / 1,613,708 alleles · 4 hom · FAF 0.0078
African/African American626 / 74,982 0.00834 hom
Remaining individuals44 / 62,488 0.0007
Admixed American37 / 59,972 0.00062
Middle Eastern2 / 6,056 0.00033
South Asian1 / 91,062 1.1e-05
European (non-Finnish)5 / 1,179,826 4.2e-06
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, East Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 0.00086 · 243 / 282,676 alleles · 2 hom · FAF 0.008
African/African American221 / 24,968 0.00892 hom
Admixed American20 / 35,416 0.00056
Remaining individuals2 / 7,218 0.00028
0 alternate alleles recorded in 5 other groups: Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), South Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000443079; MAF= 0.04431%, 715/1613708 alleles, homozygotes = 4) and has highest observed frequency in the African/African American population (AF= 0.00834867; MAF= 0.83487%, 626/74982 alleles, homozygotes = 4); grpmax FAF= 0.00780671.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000859641; MAF= 0.08596%, 243/282676 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00885133; MAF= 0.88513%, 221/24968 alleles, homozygotes = 2); grpmax FAF= 0.00797854.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0008686210640608035, 16/18420 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -174 bp
0.000
SpliceAI acceptor gainat +14 bp
0.020
SpliceAI donor lossat +260 bp
0.000
SpliceAI donor gainat +141 bp
0.000
Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.010

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingComputational evidence predicts no impact on splicing for this synonymous variant. SpliceAI assigns a maximum delta score of 0.02 (well below the 0.2 threshold), with no predicted donor gain, donor loss, acceptor gain, or acceptor loss. This supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.02: no donor/acceptor gain or loss
  • no significant splicing impact predicted.
Still missing
  • REVEL and BayesDel scores unavailable for this synonymous variant
  • limiting to splicing prediction only.
Sources
spliceai ↗
BP7 SupportingNM_016507.4:c.2964C>T is a synonymous variant (p.Phe988=) with SpliceAI predicting no splice impact (max delta score 0.02). No donor/acceptor gain or loss is predicted. The nucleotide substitution is not at a highly conserved splice consensus position and computational predictions support no effect on splicing. BP7 is met at supporting benign strength. Details ▾Hide ▴
Evidence considered
  • Synonymous variant producing p.(Phe988=).
  • SpliceAI max delta score 0.02: no donor or acceptor site gain or loss predicted.
  • Nucleotide substitution is not within the splice consensus region.
Sources
spliceai ↗
PP3 In silico prediction tools do not support a deleterious effect. REVEL and BayesDel scores are not available for this variant. SpliceAI predicts no splice impact (max delta score 0.02, well below the 0.2 threshold). No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.02: no donor/acceptor gain or loss
  • no splicing impact predicted.
  • REVEL and BayesDel scores unavailable for this synonymous variant.
Still missing
  • REVEL and BayesDel scores not computable for this synonymous variant.
Sources
spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).

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.

Recorded publications

  • Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
    Describes the ACMG/AMP standards and guidelines for variant interpretation. NM_016507.4:c.2964C>T was not mentioned in this paper. Used as the authoritative framework reference for final classification combination rules.
    Does not name this variant
    PMID 25741868 ↗
  • American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.
    Saslow D et al. · 2007
    American Cancer Society guidelines for breast cancer screening with MRI. Discusses BRCA1/BRCA2-associated breast cancer screening recommendations. NM_016507.4:c.2964C>T and CDK12 were not mentioned.
    Does not name this variant
    PMID 17392385 ↗
  • NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer.
    NSGC practice guideline for risk assessment and genetic counseling for hereditary breast and ovarian cancer. Discusses BRCA1/BRCA2 testing and counseling recommendations. NM_016507.4:c.2964C>T and CDK12 were not mentioned.
    Does not name this variant
    PMID 23188549 ↗
  • Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.
    USPSTF recommendation statement on BRCA-related cancer risk assessment and genetic testing. Discusses BRCA1/BRCA2 mutation testing in asymptomatic women. NM_016507.4:c.2964C>T and CDK12 were not mentioned.
    Does not name this variant
    PMID 24366376 ↗
  • Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.
    Patient summary of the USPSTF recommendation on BRCA-related cancer risk assessment. NM_016507.4:c.2964C>T and CDK12 were not mentioned in the available abstract.
    Does not name this variant
    PMID 24366402 ↗
  • American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.
    ASCO expert statement on collection and use of cancer family history. Discusses general oncology family history practices. NM_016507.4:c.2964C>T and CDK12 were not mentioned.
    Does not name this variant
    PMID 24493721 ↗
  • Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.
    Characterizes germline variation in 158 cancer-susceptibility genes in a healthy ancestrally diverse cohort using whole exome sequencing data. NM_016507.4:c.2964C>T and CDK12 were not mentioned in the full text.
    Does not name this variant
    PMID 24728327 ↗

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

gnomAD v4.1 715 / 1,613,708 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.020 Open source ↗
ClinVar 2 Likely benign · 1 Benign 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

Statements for reports

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

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000443079; MAF= 0.04431%, 715/1613708 alleles, homozygotes = 4) and has highest observed frequency in the African/African American population (AF= 0.00834867; MAF= 0.83487%, 626/74982 alleles, homozygotes = 4); grpmax FAF= 0.00780671.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.000859641; MAF= 0.08596%, 243/282676 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00885133; MAF= 0.88513%, 221/24968 alleles, homozygotes = 2); grpmax FAF= 0.00797854.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0008686210640608035, 16/18420 alleles, homozygotes = 0).

ClinVar

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 133856)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

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.