CDC73c.237+29_237+32delBenign

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Variant interpretation report

CDC73 c.237+29_237+32del, p.?

NM_024529.5:c.237+29_237+32del 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.

Key facts

Evidence used: 1 stand alone (benign) · 2 strong (benign) · 2 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 2 Benign
Pipeline record: 7 Jul 2026 · version 7.0.1

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): This variant has an allele frequency of 7.99% in gnomAD v2.1 (22,520/281,690 alleles, 2,860 homozygotes) and 4.74% in gnomAD v4.1 (63,137/1,331,598 alleles, 5,691 homozygotes), with a highest subpopulation frequency of 49.26% in East Asians. These frequencies far exceed the BA1 threshold of >1%. The variant is a common population polymorphism.
BS1 (strong): This variant has an allele frequency of 7.99% in gnomAD v2.1, exceeding the BS1 threshold of >0.3%. This evidence is superseded by BA1 (stand-alone benign).
BS2 (strong): This variant is observed in 2,860 homozygotes in gnomAD v2.1 and 5,691 homozygotes in gnomAD v4.1. CDC73 is associated with autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma, disorders with high penetrance. The observation of thousands of apparently healthy homozygous adults is incompatible with a pathogenic role.
BP4 (supporting): Multiple lines of computational evidence suggest no impact on splicing. SpliceAI predicts no splice impact (max delta score = 0.00) for this intronic deletion. No in silico predictors suggest a deleterious effect on gene or gene product.
BP6 (supporting): ClinVar reports this variant as Benign by two clinical laboratories (GeneDx and Center for Genomic Medicine, Rigshospitalet). Both submissions used criteria-based assessment in a clinical testing context.

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: 5

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 5

BA1Stand alone

BA1 · stand alone

This variant has an allele frequency of 7.99% in gnomAD v2.1 (22,520/281,690 alleles, 2,860 homozygotes) and 4.74% in gnomAD v4.1 (63,137/1,331,598 alleles, 5,691 homozygotes), with a highest subpopulation frequency of 49.26% in East Asians. These frequencies far exceed the BA1 threshold of >1%. The variant is a common population polymorphism.

BS1Strong

BS1 · strong

This variant has an allele frequency of 7.99% in gnomAD v2.1, exceeding the BS1 threshold of >0.3%. This evidence is superseded by BA1 (stand-alone benign).

BS2Strong

BS2 · strong

This variant is observed in 2,860 homozygotes in gnomAD v2.1 and 5,691 homozygotes in gnomAD v4.1. CDC73 is associated with autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma, disorders with high penetrance. The observation of thousands of apparently healthy homozygous adults is incompatible with a pathogenic role.

BP4Supporting

BP4 · supporting

Multiple lines of computational evidence suggest no impact on splicing. SpliceAI predicts no splice impact (max delta score = 0.00) for this intronic deletion. No in silico predictors suggest a deleterious effect on gene or gene product.

BP6Supporting

BP6 · supporting

ClinVar reports this variant as Benign by two clinical laboratories (GeneDx and Center for Genomic Medicine, Rigshospitalet). Both submissions used criteria-based assessment in a clinical testing context.

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, BS2 strong benign, BP4 supporting benign, BP6 supporting benign; combination = 1 stand-alone benign + 2 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

63,137 / 1,331,598 alleles

gnomAD v4.1: 63,137 / 1,331,598 alleles. Recorded AF 0.0474145. Recorded homozygote count 5691.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.079946; MAF= 7.99460%, 22520/281690 alleles, homozygotes = 2860) and has highest observed frequency in the East Asian population (AF= 0.492607; MAF= 49.26068%, 9728/19748 alleles, homozygotes = 2388); grpmax FAF= 0.483021.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.07179320082545888, 1322/18414 alleles, homozygotes = 174).

Applied · BA1, BS1, BS2 →

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

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

2 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

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

3 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV66464797, n = 3 times).

Context only COSMIC ↗

For specialists

Technical detail

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

28 criteria with recorded statuses: 5 met · 2 not met · 0 not assessed · 21 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 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

This variant has an allele frequency of 7.99% in gnomAD v2.1 (22,520/281,690 alleles, 2,860 homozygotes) and 4.74% in gnomAD v4.1 (63,137/1,331,598 alleles, 5,691 homozygotes), with a highest subpopulation frequency of 49.26% in East Asians, far exceeding the BA1 stand-alone benign threshold of >1%.

The variant is observed in 2,860 homozygotes in gnomAD v2.1 and 5,691 homozygotes in gnomAD v4.1. CDC73 is associated with autosomal dominant hyperparathyroidism-jaw tumor syndrome with high penetrance; the presence of thousands of homozygous individuals in population databases is incompatible with pathogenicity (BS2).

SpliceAI predicts no splice impact (max delta score = 0.00), consistent with a benign intronic variant (BP4).

ClinVar reports this variant as Benign by two clinical laboratories using criteria-based assessment (BP6).

Met · 5

BA1 Stand aloneThis variant has an allele frequency of 7.99% in gnomAD v2.1 (22,520/281,690 alleles, 2,860 homozygotes) and 4.74% in gnomAD v4.1 (63,137/1,331,598 alleles, 5,691 homozygotes), with a highest subpopulation frequency of 49.26% in East Asians. These frequencies far exceed the BA1 threshold of >1%. The variant is a common population polymorphism. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: overall AF = 7.99% (22
520/281
690 alleles
2
860 homozygotes)
gnomAD v4.1: overall AF = 4.74% (63
137/1
331
598 alleles
5
691 homozygotes)
Highest subpopulation: East Asian AF = 49.26% (v2.1)
44.30% (v4.1)
BA1 threshold of >1% is exceeded by >7-fold.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 StrongThis variant has an allele frequency of 7.99% in gnomAD v2.1, exceeding the BS1 threshold of >0.3%. This evidence is superseded by BA1 (stand-alone benign). Details ▾Hide ▴

Evidence considered

gnomAD v2.1 overall AF = 7.99%
exceeding BS1 threshold of >0.3%.
Superseded by BA1.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 StrongThis variant is observed in 2,860 homozygotes in gnomAD v2.1 and 5,691 homozygotes in gnomAD v4.1. CDC73 is associated with autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma, disorders with high penetrance. The observation of thousands of apparently healthy homozygous adults is incompatible with a pathogenic role. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 2
860 homozygotes
gnomAD v4.1: 5
691 homozygotes
CDC73-associated disorders are autosomal dominant with high penetrance.
Observation of thousands of homozygous individuals in population databases is incompatible with pathogenicity.

Sources

gnomad_v2 ↗gnomad_v4 ↗pvs1_gene_context

BP4 SupportingMultiple lines of computational evidence suggest no impact on splicing. SpliceAI predicts no splice impact (max delta score = 0.00) for this intronic deletion. No in silico predictors suggest a deleterious effect on gene or gene product. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00
no predicted donor/acceptor gain or loss.
No in silico evidence supporting a deleterious effect.

Sources

spliceai ↗

BP6 SupportingClinVar reports this variant as Benign by two clinical laboratories (GeneDx and Center for Genomic Medicine, Rigshospitalet). Both submissions used criteria-based assessment in a clinical testing context. Details ▾Hide ▴

Evidence considered

ClinVar classification: Benign (ClinVar ID 21684).
Two clinical laboratories: GeneDx (SCV001836945) and Center for Genomic Medicine
Rigshospitalet (SCV005090886).
Both submissions: criteria provided
clinical testing.

Sources

clinvar ↗

Not met · 2 · evaluated, threshold not reached

PM2 This variant is present at high frequency in population databases: gnomAD v2.1 AF = 7.99% (22,520/281,690 alleles, 2,860 homozygotes) and gnomAD v4.1 AF = 4.74% (63,137/1,331,598 alleles, 5,691 homozygotes). PM2 requires absence or very low frequency in population databases. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 overall AF = 7.99%
far exceeding PM2 threshold of <0.1%.
gnomAD v4.1 overall AF = 4.74%
far exceeding PM2 threshold.

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 Multiple lines of computational evidence do not support a deleterious effect. SpliceAI predicts no splice impact (max delta score = 0.00). REVEL and BayesDel are not available for this non-SNV variant. The computational evidence does not support pathogenicity. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00
no predicted splice impact.
REVEL and BayesDel not applicable (variant is not a single nucleotide substitution).

Sources

spliceai ↗

Not applicable · 21· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AThis variant is an intronic deletion (c.237+29_237+32del, deep intronic, +29 to +32 of intron 2) and does not fall into the default generic PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus). SpliceAI predicts no splice impact (max delta = 0.00). PVS1 cannot be applied to this variant. Details ▾Hide ▴

Evidence considered

Variant is intronic (c.237+29_237+32del)
not in canonical splice consensus.
SpliceAI max delta score = 0.00
no predicted splice impact.
pvs1_variant_assessment: apply_generic_pvs1_framework = false
suggested_default_strength = null.

Sources

pvs1_variant_assessmentpvs1_gene_contextspliceai ↗

PS1 N/ANo pathogenic variant has been identified at the same nucleotide position with a different change. This criterion requires a same-site comparator variant with established pathogenicity. Details ▾Hide ▴

Evidence considered

No same-site pathogenic comparator variant identified in ClinVar or published literature.

PS2 N/ANo de novo data are available for this variant. PS2 requires a confirmed de novo observation in a patient with the disease and no family history. Details ▾Hide ▴

Evidence considered

No de novo reports identified in ClinVar or literature.

Still missing

No de novo testing data available.

PS3 N/ANo well-established in vitro or in vivo functional studies have been identified for this specific intronic variant. PS3 requires functional evidence supporting a damaging effect. Details ▾Hide ▴

Evidence considered

No functional studies identified for this specific variant.

Still missing

No functional studies available.

PS4 N/ANo case-control or cohort studies comparing variant prevalence in affected vs. unaffected individuals are available. The variant is observed at high frequency in population databases, making it unlikely to be enriched in affected populations. Details ▾Hide ▴

Evidence considered

Variant is common in population controls (gnomAD v2.1 AF = 7.99%).

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM1 N/AThis variant is located in intron 2 (c.237+29_237+32del), not in a known functional domain or mutational hotspot. No critical functional domain or established hotspot encompasses this deep intronic position. Details ▾Hide ▴

Evidence considered

Variant is deep intronic
not in a functional domain or established mutational hotspot.

PM4 N/APM4 applies to in-frame deletions/insertions in non-repeat regions causing protein length changes. This is an intronic deletion (c.237+29_237+32del) that does not alter the protein coding sequence. Details ▾Hide ▴

Evidence considered

Variant is intronic
not a protein-coding in-frame deletion/insertion.

PM5 N/AThis variant is an intronic deletion without a defined protein residue; no amino acid change is predicted (p.?). PM5 requires a same-residue missense comparator with established pathogenicity. Per pm5_candidates.json: eligible_for_classic_pm5_search = false. Details ▾Hide ▴

Evidence considered

No protein residue context available for PM5 comparator search (p.?).

Sources

pm5_candidates

PM6 N/ANo de novo observation has been reported for this variant. PM6 requires a confirmed de novo event with confirmed maternity and paternity. Details ▾Hide ▴

Evidence considered

No de novo reports identified for this variant.

Still missing

No de novo data available.

PP1 N/ANo segregation data are available for this variant. PP1 requires cosegregation with disease in multiple affected family members. Details ▾Hide ▴

Evidence considered

No segregation studies identified.

Still missing

No family segregation data available.

PP2 N/AThis variant is an intronic deletion, not a missense variant. PP2 applies specifically to missense variants in genes with a low rate of benign missense variation. Details ▾Hide ▴

Evidence considered

Variant type is intronic deletion
not missense.

PP4 N/ANo patient phenotype or clinical data are available for this variant. PP4 requires that the variant is found in a patient whose phenotype or family history is highly specific for the disease. Details ▾Hide ▴

Evidence considered

No patient clinical data available.

Still missing

No patient phenotype data available.

PP5 N/AClinVar classifies this variant as Benign, not Pathogenic. PP5 requires a reputable source to have recently reported the variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar classification: Benign (not Pathogenic).

Sources

clinvar ↗

BS3 N/ANo well-established in vitro or in vivo functional studies have been performed on this specific variant demonstrating no damaging effect on protein function or splicing. BS3 requires functional evidence, not solely computational predictions. Details ▾Hide ▴

Evidence considered

No functional studies identified for this variant. SpliceAI prediction (BP4) is computational
not a functional study.

Still missing

No functional studies available.

BS4 N/ANo segregation data are available to assess lack of segregation with disease. BS4 requires non-segregation in affected family members. Details ▾Hide ▴

Evidence considered

No family segregation data available.

Still missing

No segregation data available.

BP1 N/AThis variant is an intronic deletion, not a missense variant. BP1 applies specifically to missense variants in genes where a truncating mechanism is the primary cause of disease. Details ▾Hide ▴

Evidence considered

Variant type is intronic deletion
not missense.

BP2 N/ANo data are available on whether this variant has been observed in trans with a known pathogenic variant. BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder. Details ▾Hide ▴

Evidence considered

No phase or co-occurrence data available.

Still missing

No trans-phase data available.

BP3 N/AThis variant is an intronic deletion, not an in-frame deletion/insertion in a repetitive region. BP3 applies to in-frame deletions/insertions in repetitive regions without known function. Details ▾Hide ▴

Evidence considered

Variant is intronic
not an in-frame deletion in a repetitive coding region.

BP5 N/ANo data are available on whether this variant is found in cases with an alternate molecular basis for disease. BP5 requires observation in a case with a clear alternate genetic cause. Details ▾Hide ▴

Evidence considered

No data on alternate molecular diagnosis in carriers.

Still missing

No data on alternate molecular diagnoses.

BP7 N/AThis variant is an intronic deletion (c.237+29_237+32del), not a synonymous (silent) variant. BP7 applies specifically to synonymous variants with no predicted splice impact. While the variant has no predicted splice impact (SpliceAI delta = 0.00), the strict definition of BP7 requires a synonymous coding change. Details ▾Hide ▴

Evidence considered

Variant is intronic
not synonymous. SpliceAI shows no splice impact but BP7 criterion definition is for synonymous variants specifically.

Sources

spliceai ↗

PS5 N/AThis variant has not been classified as Pathogenic by an expert panel or reputable source. ClinVar reports it as Benign. Details ▾Hide ▴

Evidence considered

ClinVar classification: Benign (2 clinical laboratories).

Sources

clinvar ↗

Identifiers

Gene: CDC73
Transcript: NM_024529.5
Coding (HGVS c.): NM_024529.5:c.237+29_237+32del
Protein (HGVS p.): NP_078805.3:p.?
GRCh38: chr1:193125238 TTATC>T
GRCh37: chr1:193094368 TTATC>T
ClinVar: 21684
COSMIC: COSV66464797

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…

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 CDC73 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 63,137 / 1,331,598 alleles AF 0.0474 · 5691 homozygotes · FAF 0.438

gnomAD v2.1 22,520 / 281,690 alleles AF 0.0799 · 2860 homozygotes · FAF 0.483

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.047 · 63137 / 1,331,598 alleles · 5691 hom · FAF 0.44

East Asian19116 / 43,150	0.444351 hom
Admixed American6484 / 59,628	0.11389 hom
South Asian5902 / 85,206	0.069265 hom
European (Finnish)3568 / 63,846	0.056110 hom
Remaining individuals2952 / 53,218	0.055202 hom
Middle Eastern233 / 5,504	0.0427 hom
Ashkenazi Jewish888 / 27,898	0.0329 hom
European (non-Finnish)23360 / 922,740	0.025353 hom
African/African American634 / 69,496	0.00915 hom

0 alternate alleles recorded in 1 other group: Amish.

gnomAD v2.1

AF 0.08 · 22520 / 281,690 alleles · 2860 hom · FAF 0.48

East Asian9728 / 19,748	0.492388 hom
Admixed American4389 / 35,352	0.12269 hom
South Asian2116 / 30,570	0.06983 hom
European (Finnish)1504 / 25,040	0.0651 hom
Remaining individuals420 / 7,198	0.05812 hom
Ashkenazi Jewish339 / 10,366	0.0336 hom
European (non-Finnish)3779 / 128,552	0.02947 hom
African/African American245 / 24,864	0.00994 hom

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.0474145; MAF= 4.74145%, 63137/1331598 alleles, homozygotes = 5691) and has highest observed frequency in the East Asian population (AF= 0.443013; MAF= 44.30127%, 19116/43150 alleles, homozygotes = 4351); grpmax FAF= 0.437755.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.07179320082545888, 1322/18414 alleles, homozygotes = 174).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.050

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.00
no predicted donor/acceptor gain or loss.
No in silico evidence supporting a deleterious effect.

Sources

spliceai ↗

Evidence considered

SpliceAI max delta = 0.00
no predicted splice impact.
REVEL and BayesDel not applicable (variant is not a single nucleotide substitution).

Sources

spliceai ↗

Evidence considered

Variant is intronic
not synonymous. SpliceAI shows no splice impact but BP7 criterion definition is for synonymous variants specifically.

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

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

The ACMG/AMP 2015 standards and guidelines for variant interpretation. This paper provides the classification framework and methodology used in this assessment but does not mention the specific variant NM_024529.5:c.237+29_237+32del or the CDC73 gene.
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 63,137 / 1,331,598 recorded alleles Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 2 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

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.07179320082545888, 1322/18414 alleles, homozygotes = 174).

ClinVar

This variant has been reported in ClinVar as Benign (2 clinical laboratories). (ClinVarID = 21684)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant has previously been reported in somatic cancers (COSMIC; COSV66464797, n = 3 times).