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LYFE SCIENCES
Project: HERA
NM_000548.5:c.2356-15T>A
p.?  ·  TSC2
ACMG/AMP
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Legacy Engine
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Classification rationale
1

The TSC2 c.2356-15T>A (p.?) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar, where aggregate submissions include Benign, Likely benign, and Uncertain significance classifications.

clinvar ↗
2

The variant is present at low frequency in population databases, with gnomAD v2.1 total AF 0.01435% (40/278790 alleles) and gnomAD v4.1 total AF 0.00571% (92/1610442 alleles), with no homozygotes reported.

gnomad_v2 ↗ gnomad_v4 ↗
3

In silico splicing prediction is consistent with no significant splice effect, with SpliceAI maximal delta score 0.14.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
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Rule
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Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.000143477; MAF= 0.01435%, 40/278790 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000932256; MAF= 0.09323%, 33/35398 alleles, homozygotes = 0); grpmax FAF= 0.00067374.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 5.71272e-05; MAF= 0.00571%, 92/1610442 alleles, homozygotes = 0) and has highest observed frequency in the HGDP:BASQUE population (AF= 0.0227273; MAF= 2.27273%, 1/44 alleles, homozygotes = 0); grpmax FAF= 0.00070689.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (5 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Uncertain significance (1 clinical laboratory).
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.14).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
06
Cancer hotspots
No cancer hotspot summary recorded.