Variant classification summary

NM_053056.3:c.844G>A

CCND1 · NP_444284.1:p.(Asp282Asn) · NM_053056.3

GRCh37: chr11:69466006 G>A · GRCh38: chr11:69651238 G>A

Gene: CCND1 Transcript: NM_053056.3

Final call

VUS

PM2 supporting BP4 supporting

Variant details

Gene

CCND1

Transcript

NM_053056.3

Protein

NP_444284.1:p.(Asp282Asn)

gnomAD AF

ClinVar

OncoKB

Unknown Oncogenic Effect

Classification rationale

Interpretation summary

Generated evidence synthesis

1

PM2 (Supporting): absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0 population databases.

2

BP4 (Supporting): REVEL 0.07 and SpliceAI max delta 0.001 predict no functional impact.

3

PM2 and BP4 (both supporting), combined under the generic ACMG/AMP 2015 rules, do not meet any pathogenic or benign threshold, yielding a VUS classification.

Final determination: 1 supporting pathogenic + 1 supporting benign does not satisfy any combination rule → VUS.

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: this is a missense change (p.Asp282Asn), not a null variant, so the loss-of-function mechanism PVS1 requires does not apply.	pvs1_generic_framework generic_acmg_combination_rules
PS1	Not assessed	Not assessed: no different nucleotide change producing the same p.Asp282Asn amino acid change has been established as pathogenic.	clinvar
PS2	Not assessed	Not assessed: no de novo observation with parental testing was documented for this variant.
PS3	Not assessed	Not assessed: no published functional assay data (e.g., kinase or cell-cycle assays) were available for this variant.
PS4	Not assessed	Not assessed: no affected-case series, case-control comparison, or prevalence evidence was available.
PM1	Not assessed	Not assessed: no hotspot or functional-domain annotation exists for residue 282; cancerhotspots.org returned no entry.	oncokb
PM2	Met	Met (supporting): the variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0 population databases.	gnomad_v2 gnomad_v4 gnomad_canada
PM3	Not assessed	Not assessed: no evidence places this variant in trans with a pathogenic variant for a recessive condition.
PM4	N/A	Not applicable: as a missense change, the variant does not alter protein length, which PM4 requires.	pvs1_generic_framework generic_acmg_combination_rules
PM5	Not assessed	Not assessed: no different missense change at residue 282 has been established as pathogenic.	pm5_candidates clinvar
PM6	Not assessed	Not assessed: no suspected de novo occurrence without confirmed parentage was documented.
PP1	Not assessed	Not assessed: no family segregation data, informative meioses, or variant-positive relatives were documented.
PP2	Not assessed	Not assessed: no gene-level missense constraint or benign-variation rate data were available for CCND1.
PP3	Not met	Not met: REVEL 0.07 is far below the 0.644 pathogenic-supporting threshold, indicating no predicted damaging effect.	spliceai revel
PP4	Not assessed	Not assessed: no patient phenotype or disease-specific clinical features were provided for evaluation.
PP5	Not assessed	Not assessed: the variant has no ClinVar record and no expert-panel pathogenic assertion.	clinvar
BA1	Not met	Not met: the variant is absent from population databases, so no allele frequency reaches the stand-alone benign threshold.	gnomad_v2 gnomad_v4 gnomad_canada
BS1	Not met	Not met: the variant is absent from population datasets, so it does not exceed any expected benign frequency threshold.	gnomad_v2 gnomad_v4 gnomad_canada
BS2	Not assessed	Not assessed: no observations in healthy adults, incompatible phenotypes, or homozygous individuals were available.
BS3	Not assessed	Not assessed: no functional assay data, benign or damaging, were available for this variant.
BS4	Not assessed	Not assessed: no unaffected relative carrying the variant with adequate phenotype evaluation was documented.
BP1	Not assessed	Not assessed: no evidence establishes CCND1's disease mechanism as predominantly loss-of-function, which BP1 requires.
BP2	Not assessed	Not assessed: no phase information or co-occurrence with a pathogenic variant was documented.
BP3	N/A	Not applicable: the variant is a missense change, not an in-frame indel in a repetitive region, so BP3 does not apply.	pvs1_generic_framework generic_acmg_combination_rules
BP4	Met	Met (supporting): REVEL 0.07 is below the 0.29 benign-supporting threshold, indicating no predicted functional impact.	spliceai revel
BP5	Not assessed	Not assessed: no alternative molecular diagnosis evidence or patient phenotype was available to evaluate.
BP6	Not assessed	Not assessed: the variant has no ClinVar record and no expert-panel benign assertion.	clinvar
BP7	N/A	Not applicable: BP7 applies only to synonymous variants, and this missense change alters the protein sequence.	generic_acmg_combination_rules

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