Variant classification summary

NM_000051.4:c.6975+13dupT

ATM · NP_000042.3:p.? · NM_000051.4

GRCh37: chr11:108196957 G>GT · GRCh38: chr11:108326230 G>GT

Gene: ATM Transcript: NM_000051.4

Final call

Likely Benign

BP4 supporting BP7 supporting

Variant details

Gene

ATM

Transcript

NM_000051.4

Protein

NP_000042.3:p.?

gnomAD AF

0.00010193895348475826 (v4.1)

ClinVar

Likely benign

OncoKB

Classification rationale

Interpretation summary

Generated evidence synthesis

1

BP4 (Supporting): SpliceAI max delta 0.007 is at or below the 0.1 benign threshold.

2

BP7 (Supporting): the +13 intronic position satisfies the deep-intronic (>+7) definition.

3

Combined, BP4 and BP7 Supporting satisfy Rule19, yielding Likely Benign.

Final determination: ATM VCEP v1.5 criteria-combination Rule19 classifies a variant as Likely Benign when at least two benign supporting criteria are met.

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	Not met	Not met: SpliceAI predicts no splice impact (max delta 0.007), so loss-of-function and nonsense-mediated decay are not supported.	cspec vcep_atm_pvs1_1_5 spliceai pvs1_gene_context pvs1_variant_assessment
PS1	Not assessed	Not assessed: no known pathogenic reference variant at the same position or splice motif is available for comparison.	cspec vcep_atm_ps1_1_5 spliceai
PS2	N/A	Not applicable: the ATM expert panel specifies PS2 cannot be used for this gene's conditions.	cspec
PS3	Not assessed	Not assessed: no variant-specific functional assay result for this exact duplication was available.	cspec vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1 vcep_suppl_tables1_pmid_40580951
PS4	Not assessed	Not assessed: no case-control study or effect estimate exists for this exact variant.	cspec PMID:17508274 PMID:18163131 PMID:24418350
PM1	N/A	Not applicable: the ATM expert panel excludes PM1, and the variant is intronic with no amino-acid residue.	cspec
PM2	Not met	Not met: total allele frequency 0.01019% exceeds the 0.001% PM2 threshold.	cspec gnomad_v4
PM3	Not met	Not met: group maximum allele frequency 0.032389% exceeds the 0.01% eligibility limit.	cspec vcep_atm_pm3_bp2_1_5 gnomad_v4
PM4	Not met	Not met: intronic duplication is not a stop-loss variant, the only class PM4 covers.	cspec
PM5	Not met	Not met: no observed RNA splicing impact, and SpliceAI max delta 0.007 is below the required evidence.	cspec vcep_atm_pvs1_1_5 spliceai
PM6	N/A	Not applicable: the ATM expert panel excludes PM6 for this gene's conditions.	cspec
PP1	Not assessed	Not assessed: no affected relatives or segregation results were available.	cspec
PP2	N/A	Not applicable: the ATM expert panel specifies PP2 is not used.	cspec
PP3	Not met	Not met: SpliceAI max delta 0.007 is below the 0.2 supporting threshold.	cspec spliceai
PP4	N/A	Not applicable: the ATM expert panel prohibits use of PP4.	cspec
PP5	N/A	Not applicable: no expert-panel submissions exist for this variant's ClinVar record.	cspec clinvar
BA1	Not met	Not met: group maximum allele frequency 0.032389% is below the 0.5% BA1 threshold.	cspec gnomad_v4
BS1	Not met	Not met: group maximum allele frequency 0.032389% is below the 0.05% BS1 threshold.	cspec gnomad_v4
BS2	N/A	Not applicable: the ATM expert panel specifies BS2 is not used.	cspec
BS3	Not assessed	Not assessed: no functional result demonstrating normal ATM function for this exact duplication was available.	cspec vcep_clingen_hbop_atm_supplementary_tables_1_and_2_v1 vcep_suppl_tables1_pmid_40580951
BS4	N/A	Not applicable: the ATM expert panel excludes BS4 for this gene's conditions.	cspec
BP1	N/A	Not applicable: the ATM expert panel specifies BP1 is not used.	cspec
BP2	Not assessed	Not assessed: no unaffected-carrier observation, trans variant, or phase information was available.	cspec vcep_atm_pm3_bp2_1_5
BP3	N/A	Not applicable: the ATM expert panel designates BP3 as not used.	cspec
BP4	Met	Met (Supporting): SpliceAI max delta 0.007 is at or below the 0.1 benign threshold.	cspec spliceai
BP5	N/A	Not applicable: the ATM expert panel prohibits use of BP5.	cspec
BP6	N/A	Not applicable: no expert-panel submission exists on this variant's ClinVar record.	cspec clinvar
BP7	Met	Met (Supporting): the +13 intronic position satisfies the deep-intronic (>+7) definition.	cspec

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.