Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_001126112.2(TP53):c.344A>G (p.His115Arg)

CA000126

182925 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: aac8ac5a-a8b7-4651-9186-9267f2bbb3d5

Approved on: 2021-04-12

Published on: 2021-10-11

HGVS expressions

NM_001126112.2:c.344A>G

NM_001126112.2(TP53):c.344A>G (p.His115Arg)

ENST00000269305.9:c.344A>G

ENST00000269305.8:c.344A>G

ENST00000359597.8:n.344A>G

ENST00000413465.6:n.344A>G

ENST00000420246.6:c.344A>G

ENST00000445888.6:c.344A>G

ENST00000455263.6:c.344A>G

ENST00000503591.1:c.344A>G

ENST00000505014.5:n.600A>G

ENST00000508793.5:c.344A>G

ENST00000509690.5:c.-21-789A>G

ENST00000514944.5:c.96+357A>G

ENST00000604348.5:c.344A>G

ENST00000610292.4:c.227A>G

ENST00000610538.4:c.227A>G

ENST00000615910.4:n.340A>G

ENST00000617185.4:c.344A>G

ENST00000619485.4:c.227A>G

ENST00000620739.4:c.227A>G

ENST00000622645.4:c.227A>G

ENST00000635293.1:c.227A>G

NM_000546.5:c.344A>G

NM_001126113.2:c.344A>G

NM_001126114.2:c.344A>G

NM_001126118.1:c.227A>G

NM_001276695.1:c.227A>G

NM_001276696.1:c.227A>G

NM_001276760.1:c.227A>G

NM_001276761.1:c.227A>G

NM_001276695.2:c.227A>G

NM_001276696.2:c.227A>G

NM_001276760.2:c.227A>G

NM_001276761.2:c.227A>G

NM_000546.6:c.344A>G

NM_001126112.3:c.344A>G

NM_001126113.3:c.344A>G

NM_001126114.3:c.344A>G

NM_001126118.2:c.227A>G

NM_001276695.3:c.227A>G

NM_001276696.3:c.227A>G

NM_001276760.3:c.227A>G

NM_001276761.3:c.227A>G

NC_000017.11:g.7676025T>C

CM000679.2:g.7676025T>C

NC_000017.10:g.7579343T>C

CM000679.1:g.7579343T>C

NC_000017.9:g.7520068T>C

NG_017013.2:g.16526A>G

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS3 BP4 PM2_Supporting

BA1 BS2 BS4 BS1 PS4 PS3 PS1 PP3 PM1 PM5 PM6

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). Transactivation assays show [retained/supertransactivation] function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.344A>G (p.His115Arg) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, BS3, BP4. In this case, PM2_Supporting should not be applied as there is sufficient evidence codes for variant to meet Likely Benign classification.

BS3

Present in Kato (97 = Functional)/p53WTNutlin3 Z-score < 0.61 (-0,087) and Etoposide Z-score > -0.21 (0,609)

BP4

Align GVGD Class C0; BayesDel = 0.0464. aGVGD (Zebrafish; Class C0 or C15 is considered evidence of non-pathogenicity) and BayesDel <0.16 is considered evidence on non-pathogenicity

PM2_Supporting

Absent from population databases

BA1