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]

x This classification has been retracted/unpublished!

Variant: NM_001276761.2:c.365_370del

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA915940817

973858 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 04670dbf-dcc3-4cec-8727-691d183eec54

Approved on: 2021-02-22

Published on: 2021-10-11

HGVS expressions

NM_001276761.2:c.365_370del

NC_000017.11:g.7675125_7675130del

CM000679.2:g.7675125_7675130del

NC_000017.10:g.7578443_7578448del

CM000679.1:g.7578443_7578448del

NC_000017.9:g.7519168_7519173del

NG_017013.2:g.17421_17426del

ENST00000503591.2:c.482_487del

ENST00000508793.6:c.482_487del

ENST00000509690.6:c.86_91del

ENST00000514944.6:c.203_208del

ENST00000604348.6:c.461_466del

ENST00000269305.9:c.482_487del

ENST00000269305.8:c.482_487del

ENST00000359597.8:c.482_487del

ENST00000413465.6:c.482_487del

ENST00000420246.6:c.482_487del

ENST00000445888.6:c.482_487del

ENST00000455263.6:c.482_487del

ENST00000504290.5:c.86_91del

ENST00000504937.5:c.86_91del

ENST00000505014.5:n.738_743del

ENST00000508793.5:c.482_487del

ENST00000509690.5:c.86_91del

ENST00000510385.5:c.86_91del

ENST00000514944.5:c.203_208del

ENST00000610292.4:c.365_370del

ENST00000610538.4:c.365_370del

ENST00000610623.4:c.5_10del

ENST00000615910.4:c.449_454del

ENST00000617185.4:c.482_487del

ENST00000618944.4:c.5_10del

ENST00000619186.4:c.5_10del

ENST00000619485.4:c.365_370del

ENST00000620739.4:c.365_370del

ENST00000622645.4:c.365_370del

ENST00000635293.1:c.365_370del

NM_000546.5:c.482_487del

NM_001126112.2:c.482_487del

NM_001126113.2:c.482_487del

NM_001126114.2:c.482_487del

NM_001126115.1:c.86_91del

NM_001126116.1:c.86_91del

NM_001126117.1:c.86_91del

NM_001126118.1:c.365_370del

NM_001276695.1:c.365_370del

NM_001276696.1:c.365_370del

NM_001276697.1:c.5_10del

NM_001276698.1:c.5_10del

NM_001276699.1:c.5_10del

NM_001276760.1:c.365_370del

NM_001276761.1:c.365_370del

NM_001276695.2:c.365_370del

NM_001276696.2:c.365_370del

NM_001276697.2:c.5_10del

NM_001276698.2:c.5_10del

NM_001276699.2:c.5_10del

NM_001276760.2:c.365_370del

NM_000546.6:c.482_487del

NM_001126112.3:c.482_487del

NM_001126113.3:c.482_487del

NM_001126114.3:c.482_487del

NM_001126115.2:c.86_91del

NM_001126116.2:c.86_91del

NM_001126117.2:c.86_91del

NM_001126118.2:c.365_370del

NM_001276695.3:c.365_370del

NM_001276696.3:c.365_370del

NM_001276697.3:c.5_10del

NM_001276698.3:c.5_10del

NM_001276699.3:c.5_10del

NM_001276760.3:c.365_370del

NM_001276761.3:c.365_370del

Uncertain Significance

PM2_Supporting PM5 PS4_Supporting

PP1 PM1 PM6 BS1 BS4 BS3 BS2 BP2 BA1 PS2 PS3

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

This variant has been reported in 1 proband meeting Classic LFS criteria (PS4_Supporting; internal clinical contributor). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There are 2 TP53 pathogenic variants (p.Y163C, p.A161D) previously reported at this codon (PM5; ClinVar ID 127814, 422295). In summary, the clinical significance of TP53 c.482_487del (p.Ala161_Tyr163delinsAsp) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM5, PM2_Supporting, PS4_Supporting.

PM2_Supporting

Variant absent from database

PM5

Disrupts the p.Tyr163 amino acid residue in TP53. This variant is classified as P by VCEP. Other variants that disrupt this residue have been determined to be pathogenic (PMID: 8164043, 18685109, 19556618, 12826609, 16861262). Suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. A161 is curated as LP using VCEP ruleset.

PS4_Supporting

Proband in internal clinical case meets Classical criteria = 1 point. No other cases found in the literature

PP1

No cases in the literature and proband's family not tested

PM1

Can't use

PM6

No de novo cases found

BS1

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

BS4

No cases in the literature and proband's family not tested

BS3

Can't use

BS2

Not found in FLOSSIES

BP2

No cases in literature

BA1

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

PS2

No de novo cases found

PS3

Can't use

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.