Variant classification summary

NM_053056.3:c.839_841del

CCND1 · NP_444284.1:p.(Glu280del) · NM_053056.3

GRCh37: chr11:69465987 AGAG>A · GRCh38: chr11:69651219 AGAG>A

Gene: CCND1 Transcript: NM_053056.3

Final call

Likely Benign

BP3 supporting BP4 supporting

Variant details

Gene

CCND1

Transcript

NM_053056.3

Protein

NP_444284.1:p.(Glu280del)

gnomAD AF

0.00018435794688991268 (v4.1)

ClinVar

Likely benign

OncoKB

Unknown Oncogenic Effect

Classification rationale

Interpretation summary

Generated evidence synthesis

1

BP3 (Supporting): in-frame deletion of one codon (p.Glu280del) within a low-complexity poly-glutamate repeat region without known function.

2

BP4 (Supporting): SpliceAI max delta 0.001, below the 0.1 threshold indicating no splice impact.

3

Final classification: Likely Benign, per the generic ACMG/AMP 2015 rule satisfied by two supporting benign (BP) criteria.

Final determination: Generic ACMG/AMP 2015 fallback rule: two supporting-strength benign criteria (2 BP) combine to yield a Likely Benign classification.

Criteria assessment

ACMG/AMP criteria review

Criteria shown when status is available

All criteria require review: For research and educational purposes only.

Criterion	Status	Rationale	Evidence used
PVS1	N/A	Not applicable: in-frame single-codon deletion, not a null variant (nonsense, frameshift, or splice-site) expected to trigger nonsense-mediated decay.	pvs1_generic_framework generic_acmg_combination_rules
PS1	N/A	Not applicable: in-frame deletion, so no amino acid change exists to compare against a previously established pathogenic variant at this residue.	generic_acmg_combination_rules
PS2	Not assessed	Not assessed: no de novo observation or parental testing results were available to establish confirmed de novo occurrence.
PS3	Not assessed	Not assessed: no validated functional assay data for this variant were available.
PS4	Not assessed	Not assessed: no case-control enrichment or affected-case count data for this exact variant were available.
PM1	N/A	Not applicable: in-frame deletion, so no altered residue exists to evaluate for mutational hot-spot or critical-domain membership.	generic_acmg_combination_rules
PM2	Not met	Not met: present in population databases — gnomAD v4.1 reports 295 alleles and one homozygote.	gnomad_v2 gnomad_v4 gnomad_canada
PM3	Not assessed	Not assessed: no evidence of a second disease-causing allele in trans was available.
PM4	Not met	Not met: the in-frame deletion falls in a low-complexity poly-glutamate repeat, failing the non-repeat-region prerequisite (BP3 governs instead).	generic_acmg_combination_rules clinvar gnomad_v2 spliceai
PM5	N/A	Not applicable: in-frame deletion, so no missense change exists to compare against a pathogenic missense at the same residue.	generic_acmg_combination_rules
PM6	Not assessed	Not assessed: no de novo observation without parental confirmation was documented.
PP1	Not assessed	Not assessed: no segregation data from affected or unaffected relatives were available.
PP2	N/A	Not applicable: in-frame deletion, not a missense variant, so the missense-constraint criterion does not apply.	generic_acmg_combination_rules
PP3	Not met	Not met: SpliceAI max delta 0.001 vs the 0.2 threshold required for PP3.	spliceai
PP4	Not assessed	Not assessed: no patient phenotype description was available.
PP5	Not met	Not met: ClinVar's Likely benign entry is from one laboratory with zero review stars, not an expert-panel classification.	clinvar
BA1	Not met	Not met: gnomAD maximum population allele frequency 0.0015 vs the 5% BA1 threshold.	gnomad_v2 gnomad_v4
BS1	Not assessed	Not assessed: no disease prevalence or gene-specific maximum credible allele frequency was available to set a threshold.	gnomad_v2 gnomad_v4 clinvar
BS2	Not assessed	Not assessed: no age, phenotype, or health-status information for the gnomAD homozygote was available.	gnomad_v4
BS3	Not assessed	Not assessed: no validated functional assay data showing normal function were available.
BS4	Not assessed	Not assessed: no unaffected relatives with genotype and phenotype data were documented.
BP1	N/A	Not applicable: in-frame deletion, not a missense variant, so the truncation-mechanism criterion does not apply.	generic_acmg_combination_rules
BP2	Not assessed	Not assessed: no phase or segregation data showing the variant in trans or cis with a pathogenic variant.
BP3	Met	Met (supporting): in-frame deletion of one codon within a low-complexity poly-glutamate repeat with no known function. Flagged for human review: the repeat lies in a PEST-like region with general roles in protein stability.	generic_acmg_combination_rules clinvar gnomad_v2 spliceai
BP4	Met	Met (supporting): SpliceAI max delta 0.001 vs the 0.1 threshold for BP4.	spliceai
BP5	Not assessed	Not assessed: no alternative molecular diagnosis was established for the patient.
BP6	Not met	Not met: ClinVar's Likely benign entry is from one laboratory with zero review stars, not an expert-panel benign classification.	clinvar
BP7	N/A	Not applicable: not a synonymous variant, since the encoded protein sequence is altered.	generic_acmg_combination_rules

Disclaimer: The content and results provided by LYFE Sciences are for research and educational purposes only and must not be used as a substitute for professional medical judgment, diagnosis, or treatment. Always consult a qualified healthcare professional before making any clinical decisions.