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.145G>C (p.Asp49His)

CA000057

135948 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3ae5f394-d710-4984-8d13-7c585ade67dc

HGVS expressions

NM_001126112.2:c.145G>C

NM_001126112.2(TP53):c.145G>C (p.Asp49His)

NC_000017.11:g.7676224C>G

CM000679.2:g.7676224C>G

NC_000017.10:g.7579542C>G

CM000679.1:g.7579542C>G

NC_000017.9:g.7520267C>G

NG_017013.2:g.16327G>C

ENST00000269305.9:c.145G>C

ENST00000269305.8:c.145G>C

ENST00000359597.8:n.145G>C

ENST00000413465.6:n.145G>C

ENST00000420246.6:c.145G>C

ENST00000445888.6:c.145G>C

ENST00000455263.6:c.145G>C

ENST00000503591.1:c.145G>C

ENST00000505014.5:n.401G>C

ENST00000508793.5:c.145G>C

ENST00000509690.5:c.-21-988G>C

ENST00000514944.5:c.96+158G>C

ENST00000604348.5:c.145G>C

ENST00000610292.4:c.28G>C

ENST00000610538.4:c.28G>C

ENST00000615910.4:n.145G>C

ENST00000617185.4:c.145G>C

ENST00000619485.4:c.28G>C

ENST00000620739.4:c.28G>C

ENST00000622645.4:c.28G>C

ENST00000635293.1:c.28G>C

NM_000546.5:c.145G>C

NM_001126113.2:c.145G>C

NM_001126114.2:c.145G>C

NM_001126118.1:c.28G>C

NM_001276695.1:c.28G>C

NM_001276696.1:c.28G>C

NM_001276760.1:c.28G>C

NM_001276761.1:c.28G>C

NM_001276695.2:c.28G>C

NM_001276696.2:c.28G>C

NM_001276760.2:c.28G>C

NM_001276761.2:c.28G>C

NM_000546.6:c.145G>C

NM_001126112.3:c.145G>C

NM_001126113.3:c.145G>C

NM_001126114.3:c.145G>C

NM_001126118.2:c.28G>C

NM_001276695.3:c.28G>C

NM_001276696.3:c.28G>C

NM_001276760.3:c.28G>C

NM_001276761.3:c.28G>C

NM_000546.6(TP53):c.145G>C (p.Asp49His)

Likely Benign

BP4 BS2_Supporting

BS4 BS3 BS1 BP2 BP1 BP5 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM3 PM1 PM5 BA1 PM6 PM2

Evidence Links 2

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributor). In summary, TP53 c.125G>C (p.D49H) 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: BP4, BS2_Supporting.

BP4

BayesDel -0.03 and AGVGD is C0

BS2_Supporting

3 female individuals cancer free by age 60 observed with this variant.

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

Kato et al shows non functional transactivation, but Giacomelli shows no DN and no loss of growth suppression.

This variant shows non-functional transactivation in yeast studies. PubMed:12826609

This variant shows no dominant negative effect and no loss of function. PubMed:30224644

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP1

Not used for TP53

BP5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS4

No individuals meeting LFS or Chompret criteira.

PS3

Kato et al shows non functional transactivation, but Giacomelli shows no DN and no loss of growth suppression.

This variant shows non-functional transactivation in yeast studies. PubMed:12826609

This variant shows no dominant negative effect and no loss of function. PubMed:30224644

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP2

Not used for TP53

PM3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM1

Not present in cancerhotspots.org

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM6

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

1 allele present in non-cancer dataset. Must be absent to apply PM2.

Approved on: 2022-01-10

Published on: 2022-01-10

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