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CDC73c.424-28A>GBenign
Print report
Variant interpretation report

CDC73 c.424-28A>G, p.?

NM_024529.5:c.424-28A>G NP_078805.3:p.? View identifiers
Classification
Benign

Variant description:

No variant summary was recorded for this case.

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

Benign.A benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About CDC73

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: 4
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 4
BA1Stand alone
BA1 · stand alone

This variant has a maximum population allele frequency exceeding 1%. gnomAD v2.1 grpmax FAF is 1.056% (Ashkenazi Jewish AF=1.32%) and gnomAD v4.1 grpmax FAF is 1.147% (Ashkenazi Jewish AF=1.39%). Additionally, 10 homozygotes are observed in gnomAD v2.1 and 102 homozygotes in gnomAD v4.1, incompatible with a highly penetrant dominant disorder.

BS1Strong
BS1 · strong

This variant is present in gnomAD at an allele frequency well above 0.3%. gnomAD v2.1 overall AF is 0.76% (2161/282588 alleles) and gnomAD v4.1 overall AF is 0.99% (15162/1526634 alleles), both exceeding the BS1 threshold.

BP4Supporting
BP4 · supporting

SpliceAI predicts no significant splice impact (max delta score = 0.07). Multiple lines of in silico evidence (absence of splice-altering prediction, no REVEL/BayesDel scores for intronic variant) support a benign interpretation.

BP6Supporting
BP6 · supporting

This variant has been reported in ClinVar as Benign by a clinical laboratory (Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital; SCV002760434) with criteria provided. While this is a single submitter (1-star), the classification is Benign with documented criteria.

Recorded classification: 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: BA1 stand-alone benign, BS1 strong benign, BP4 supporting benign, BP6 supporting benign; combination = 1 stand-alone benign + 1 strong benign + 2 supporting benign, which maps to 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
15,162 / 1,526,634 alleles

gnomAD v4.1: 15,162 / 1,526,634 alleles. Recorded AF 0.00993165. Recorded homozygote count 102.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00764718; MAF= 0.76472%, 2161/282588 alleles, homozygotes = 10) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.013229; MAF= 1.32290%, 137/10356 alleles, homozygotes = 0); grpmax FAF= 0.0105605.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00890239930517859, 164/18422 alleles, homozygotes = 3).

Applied · BA1, BS1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.070 maximum delta

Recorded SpliceAI maximum delta score: 0.070. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
1 reported laboratory submissions

1 Benign. ClinVar API review status: criteria provided, single submitter.

Applied · BP6 → ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
No matching record reported

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

Context only COSMIC ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 4 met · 7 not met · 7 not assessed · 8 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

This variant has been observed in population databases at an allele frequency exceeding the BA1 threshold: gnomAD v2.1 grpmax FAF 1.056% (Ashkenazi Jewish AF 1.32%, 10 homozygotes) and gnomAD v4.1 grpmax FAF 1.147% (Ashkenazi Jewish AF 1.39%, 102 homozygotes). This frequency and the presence of homozygotes is incompatible with a highly penetrant dominant disorder. BA1 (stand-alone benign) is met.

This variant is present in gnomAD at an allele frequency exceeding the BS1 threshold: gnomAD v2.1 overall AF 0.76% and gnomAD v4.1 overall AF 0.99%, both well above 0.3%. BS1 (strong benign) is met.

SpliceAI predicts no significant splice impact for this intronic variant (max delta score 0.07). No in silico evidence supports a deleterious effect. BP4 (supporting benign) is met.

This variant has been reported in ClinVar as Benign by a clinical laboratory (SCV002760434, Center for Genomic Medicine, Rigshospitalet) with criteria provided. BP6 (supporting benign) is met.

No pathogenic criteria are met. The variant is an intronic substitution (c.424-28A>G) with no splice impact, absent from COSMIC, and has no functional or segregation data supporting pathogenicity.

Met · 4

BA1 Stand aloneThis variant has a maximum population allele frequency exceeding 1%. gnomAD v2.1 grpmax FAF is 1.056% (Ashkenazi Jewish AF=1.32%) and gnomAD v4.1 grpmax FAF is 1.147% (Ashkenazi Jewish AF=1.39%). Additionally, 10 homozygotes are observed in gnomAD v2.1 and 102 homozygotes in gnomAD v4.1, incompatible with a highly penetrant dominant disorder. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 grpmax FAF=1.056%
  • Ashkenazi Jewish AF=1.32%
  • 10 homozygotes
  • gnomAD v4.1 grpmax FAF=1.147%
  • Ashkenazi Jewish AF=1.39%
  • 102 homozygotes.
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 StrongThis variant is present in gnomAD at an allele frequency well above 0.3%. gnomAD v2.1 overall AF is 0.76% (2161/282588 alleles) and gnomAD v4.1 overall AF is 0.99% (15162/1526634 alleles), both exceeding the BS1 threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 total AF=0.76% (>0.3%)
  • gnomAD v4.1 total AF=0.99% (>0.3%).
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingSpliceAI predicts no significant splice impact (max delta score = 0.07). Multiple lines of in silico evidence (absence of splice-altering prediction, no REVEL/BayesDel scores for intronic variant) support a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.07
  • no evidence of deleterious splicing effect.
Sources
spliceai ↗
BP6 SupportingThis variant has been reported in ClinVar as Benign by a clinical laboratory (Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital; SCV002760434) with criteria provided. While this is a single submitter (1-star), the classification is Benign with documented criteria. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 1802764: Benign
  • criteria provided
  • single submitter (SCV002760434).
Sources
clinvar ↗

Not met · 7 · evaluated, threshold not reached

PS3 No functional data available for NM_024529.5:c.424-28A>G. No experimental studies testing this variant or a systematically characterized range that includes it were identified. Details ▾Hide ▴
Evidence considered
  • No functional studies identified in literature or databases.
Still missing
  • No functional data for this intronic variant.
PS4 No case-control or cohort data demonstrating enrichment of this variant in affected individuals compared to controls. Details ▾Hide ▴
Evidence considered
  • No case-control data available.
Still missing
  • No prevalence data in affected cohorts.
PM2 This variant is present in gnomAD v2.1 at 0.76% (2161/282588 alleles, 10 homozygotes) and in gnomAD v4.1 at 0.99% (15162/1526634 alleles, 102 homozygotes), well above the 0.1% PM2 threshold for absence from population databases. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 AF=0.7647%
  • gnomAD v4.1 AF=0.9932%
  • far exceeds PM2 <0.1% threshold.
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP3 SpliceAI max delta score is 0.07, which does not support a deleterious splicing effect. No other in silico scores are available (REVEL and BayesDel are not applicable to intronic variants). Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.07
  • no evidence of deleterious splicing. REVEL/BayesDel not applicable.
Sources
spliceai ↗
PP5 ClinVar classifies this variant as Benign, not Pathogenic. PP5 requires a pathogenic classification from a reputable source. The single ClinVar submission (SCV002760434, Center for Genomic Medicine, Rigshospitalet) reports Benign. Details ▾Hide ▴
Evidence considered
  • ClinVar Variation ID 1802764: Benign (1 submitter
  • criteria provided single submitter).
Sources
clinvar ↗
BS2 No specific observation in healthy adult controls documented for this variant in the context of full penetrance expected at early age. While the variant has many gnomAD homozygotes, BS2 requires documented observation in healthy adults for a disorder expected to be fully penetrant at an early age, which is better captured by BA1 population frequency data. Details ▾Hide ▴
Evidence considered
  • No specific healthy adult control data beyond gnomAD population frequencies.
BS3 No functional data demonstrating no damaging effect for this variant. SpliceAI max delta 0.07 does not constitute a functional assay showing no protein effect — it is in silico prediction, addressable under BP4/BP7. Details ▾Hide ▴
Evidence considered
  • No functional studies identified for this variant.
Still missing
  • No experimental functional data.

Not assessed · 7 · no assessment recorded

PS2 No de novo data available for this variant. Details ▾Hide ▴
Still missing
  • No de novo testing data in case materials.
PM6 No de novo data available for this variant. Details ▾Hide ▴
Still missing
  • No de novo testing data in case materials.
PP1 No segregation data available for this variant. Details ▾Hide ▴
Still missing
  • No family segregation data.
PP4 No patient phenotype or clinical data available for this case. Details ▾Hide ▴
Still missing
  • No clinical phenotype data provided.
BS4 No segregation data available for non-segregation with disease in affected family members. Details ▾Hide ▴
Still missing
  • No family segregation data.
BP2 No data on observation in trans with a pathogenic variant for a fully penetrant dominant disorder. The 10 homozygotes in gnomAD are addressed under BA1. Details ▾Hide ▴

No further detail was recorded.

BP5 No case data available for an alternative molecular basis of disease. Details ▾Hide ▴
Still missing
  • No case data for alternative molecular basis.
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is an intronic variant (c.424-28A>G, intron 5) with SpliceAI max delta 0.07, indicating no significant splice impact. Does not meet null variant criteria (nonsense, frameshift, or canonical ±1,2 splice consensus). Details ▾Hide ▴
Evidence considered
  • Intronic variant at -28 position
  • SpliceAI max delta 0.07
  • no predicted splicing effect.
Sources
pvs1_generic_framework ↗spliceai ↗
PS1 N/ANot a missense variant; intronic change cannot be compared to a known pathogenic missense change at the same amino acid position. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • PS1 requires same-residue missense comparator.
PM1 N/AIntronic variant at -28 position in intron 5 with SpliceAI max delta 0.07, indicating no significant splice impact. Not located in a mutational hot spot or critical functional domain. Details ▾Hide ▴
Evidence considered
  • Deep intronic variant
  • SpliceAI shows no significant splice effect
  • not in a characterized functional domain.
Sources
spliceai ↗
PM5 N/AIntronic variant has no amino acid residue context; PM5 requires a same-residue missense comparator. No candidates identified in ClinVar. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • no residue for PM5 comparison.
PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation. This is an intronic variant. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • PP2 is missense-specific.
BP1 N/ABP1 applies to missense variants in genes where a truncating mechanism is primary. This is an intronic variant, not a missense change. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • BP1 is missense-specific.
BP7 N/ABP7 applies to synonymous variants at non-conserved nucleotides with no predicted splice impact. This is an intronic substitution, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • BP7 applies to synonymous variants.
PS5 N/APS5 requires an established pathogenic variant from a reputable source. This intronic variant has no functional consequence and no established pathogenicity mechanism; not a de novo candidate for this criterion. Details ▾Hide ▴
Evidence considered
  • Intronic variant with no splice impact
  • no established pathogenicity.

Identifiers

Gene
CDC73
Transcript
NM_024529.5
Coding (HGVS c.)
NM_024529.5:c.424-28A>G
Protein (HGVS p.)
NP_078805.3:p.?
GRCh38
chr1:193138057 A>G
GRCh37
chr1:193107187 A>G
ClinVar
1802764

Gene diagram

Every interpreted variant in CDC73, mapped onto the exon structure of NM_024529.5. Select a row to find it on the plot.

CDC73NM_024529.5
Fetching transcript structure from UCSC…
gnomAD v4.1 15,162 / 1,526,634 alleles AF 0.00993 · 102 homozygotes · FAF 0.0115
gnomAD v2.1 2,161 / 282,588 alleles AF 0.00765 · 10 homozygotes · FAF 0.0106
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.0099 · 15162 / 1,526,634 alleles · 102 hom · FAF 0.011
Ashkenazi Jewish403 / 29,060 0.0143 hom
European (Finnish)789 / 63,974 0.0125 hom
European (non-Finnish)12802 / 1,100,320 0.01288 hom
Remaining individuals519 / 59,528 0.00873 hom
Middle Eastern36 / 5,880 0.0061
Admixed American304 / 59,898 0.00511 hom
South Asian172 / 89,392 0.00191 hom
African/African American137 / 73,218 0.00191 hom
0 alternate alleles recorded in 2 other groups: Amish, East Asian.

gnomAD v2.1

AF 0.0076 · 2161 / 282,588 alleles · 10 hom · FAF 0.011
Ashkenazi Jewish137 / 10,356 0.013
European (Finnish)285 / 25,116 0.0112 hom
European (non-Finnish)1428 / 129,084 0.0116 hom
Remaining individuals56 / 7,218 0.0078
Admixed American159 / 35,394 0.00451 hom
South Asian59 / 30,548 0.00191 hom
African/African American37 / 24,920 0.0015
0 alternate alleles recorded in 1 other group: East Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00993165; MAF= 0.99317%, 15162/1526634 alleles, homozygotes = 102) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0138679; MAF= 1.38679%, 403/29060 alleles, homozygotes = 3); grpmax FAF= 0.011466.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00764718; MAF= 0.76472%, 2161/282588 alleles, homozygotes = 10) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.013229; MAF= 1.32290%, 137/10356 alleles, homozygotes = 0); grpmax FAF= 0.0105605.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00890239930517859, 164/18422 alleles, homozygotes = 3).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat +15 bp
0.070
SpliceAI acceptor gainat -120 bp
0.010
SpliceAI donor lossat +249 bp
0.000
SpliceAI donor gainat -68 bp
0.010
Pangolin splice lossmagnitude shown
-0.030
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingSpliceAI predicts no significant splice impact (max delta score = 0.07). Multiple lines of in silico evidence (absence of splice-altering prediction, no REVEL/BayesDel scores for intronic variant) support a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.07
  • no evidence of deleterious splicing effect.
Sources
spliceai ↗
PP3 SpliceAI max delta score is 0.07, which does not support a deleterious splicing effect. No other in silico scores are available (REVEL and BayesDel are not applicable to intronic variants). Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta 0.07
  • no evidence of deleterious splicing. REVEL/BayesDel not applicable.
Sources
spliceai ↗
BP7 N/ABP7 applies to synonymous variants at non-conserved nucleotides with no predicted splice impact. This is an intronic substitution, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • BP7 applies to synonymous variants.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).

1 paper record 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.
    Richards S et al. · 2015
    This is the ACMG/AMP 2015 standards and guidelines for sequence variant interpretation (Richards et al.). The paper defines the generic classification framework and criteria. NM_024529.5:c.424-28A>G was not identified in this paper.
    Does not name this variant
    PMID 25741868 ↗

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

gnomAD v4.1 15,162 / 1,526,634 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.070 Open source ↗
ClinVar 1 Benign Open source ↗
COSMIC Captured COSMIC 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= 0.00993165; MAF= 0.99317%, 15162/1526634 alleles, homozygotes = 102) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0138679; MAF= 1.38679%, 403/29060 alleles, homozygotes = 3); grpmax FAF= 0.011466.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00764718; MAF= 0.76472%, 2161/282588 alleles, homozygotes = 10) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.013229; MAF= 1.32290%, 137/10356 alleles, homozygotes = 0); grpmax FAF= 0.0105605.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.00890239930517859, 164/18422 alleles, homozygotes = 3).

ClinVar

This variant has been reported in ClinVar as Benign (1 clinical laboratory). (ClinVarID = 1802764)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).

Somatic

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