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LYFE SCIENCES
Project: HERA
NM_000548.5:c.3884-17C>G
p.?  ·  TSC2
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Classification rationale
1

The TSC2 NM_000548.5:c.3884-17C>G (NP_000539.2:p.?) variant has been reported in ClinVar predominantly as benign or likely benign, without an expert panel review.

clinvar ↗
2

This variant is present in population databases, including gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada, with the highest observed frequency of 0.65789% (6/912) in the Amish population in gnomAD v4.1, which is above the default BS1 threshold of 0.3% and below the default BA1 threshold of 1%.

gnomad_v2 ↗ gnomad_v4 ↗ gnomad_canada ↗
3

In silico splicing analysis does not support a deleterious effect, as SpliceAI predicts no significant splice impact with a maximum delta score of 0.00.

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
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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= 0.00061533; MAF= 0.06153%, 131/212894 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00125942; MAF= 0.12594%, 115/91312 alleles, homozygotes = 0); grpmax FAF= 0.00162279.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000896273; MAF= 0.08963%, 1407/1569834 alleles, homozygotes = 0) and has highest observed frequency in the Amish population (AF= 0.00657895; MAF= 0.65789%, 6/912 alleles, homozygotes = 0); grpmax FAF= 0.00109091.
gnomAD CanadaThis variant is present in gnomAD-Canada v1.0 (AF= 0.000434499; MAF= 0.04345%, 8/18412 alleles, homozygotes = 0) and has highest observed frequency in the amr population (AF= 0.00119332; grpmax FAF95= 0).
gnomAD v2 ↗ gnomAD v4 ↗ gnomAD 🇨🇦 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (6 clinical laboratories) and as Likely benign (4 clinical laboratories) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 49513)
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 = 0.00).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV104375921, n = 2 times).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.