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_001276761.1:c.802+1G>A

CA397836247

633606 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e5597807-7124-425a-b33a-5c6af85c5edc

HGVS expressions

NM_001276761.1:c.802+1G>A

NC_000017.11:g.7673700C>T

CM000679.2:g.7673700C>T

NC_000017.10:g.7577018C>T

CM000679.1:g.7577018C>T

NC_000017.9:g.7517743C>T

NG_017013.2:g.18851G>A

NM_000546.5:c.919+1G>A

NM_001126112.2:c.919+1G>A

NM_001126113.2:c.919+1G>A

NM_001126114.2:c.919+1G>A

NM_001126115.1:c.523+1G>A

NM_001126116.1:c.523+1G>A

NM_001126117.1:c.523+1G>A

NM_001126118.1:c.802+1G>A

NM_001276695.1:c.802+1G>A

NM_001276696.1:c.802+1G>A

NM_001276697.1:c.442+1G>A

NM_001276698.1:c.442+1G>A

NM_001276699.1:c.442+1G>A

NM_001276760.1:c.802+1G>A

NM_001276695.2:c.802+1G>A

NM_001276696.2:c.802+1G>A

NM_001276697.2:c.442+1G>A

NM_001276698.2:c.442+1G>A

NM_001276699.2:c.442+1G>A

NM_001276760.2:c.802+1G>A

NM_001276761.2:c.802+1G>A

ENST00000269305.8:c.919+1G>A

ENST00000359597.8:n.919+1G>A

ENST00000413465.6:n.782+481G>A

ENST00000420246.6:c.919+1G>A

ENST00000445888.6:c.919+1G>A

ENST00000455263.6:c.919+1G>A

ENST00000504290.5:c.523+1G>A

ENST00000504937.5:c.523+1G>A

ENST00000509690.5:c.523+1G>A

ENST00000510385.5:c.523+1G>A

ENST00000610292.4:c.802+1G>A

ENST00000610538.4:c.802+1G>A

ENST00000610623.4:c.442+1G>A

ENST00000615910.4:n.886+1G>A

ENST00000617185.4:c.919+1G>A

ENST00000618944.4:c.442+1G>A

ENST00000619186.4:c.442+1G>A

ENST00000619485.4:c.802+1G>A

ENST00000620739.4:c.802+1G>A

ENST00000622645.4:c.802+1G>A

ENST00000635293.1:c.802+1G>A

Likely Pathogenic

PM2_Supporting PVS1_Strong PM6_Supporting

PS2 PS4

Evidence Links 1

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

The c.919+1G>A is canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There is a proband with a de novo observation with bilateral, metachronous breast cancer without mention of parental confirmation (PM6_Supporting; PMID: 28509937). In summary, TP53 c.919+1G>A meets criteria to be classified as likely pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PVS1_Strong, PM2_Supporting, PM6_Supporting.

PM2_Supporting

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

PVS1_Strong

Canonical splice variant

PM6_Supporting

This variant was seen in a female with a personal history of bilateral, metachronous breast cancer diagnoses at age 33 and 36. Points = 0.5

PS2

Clinical case submitted by EP member: proband w/breast cancer at 26 (not used since case is unpublished and not in ClinVar)

PS4

Variant in several probands with breast cancer but none meet Chompret criteria.

Proband with breast cancer at 32 yrs. No known family history, but does not appear that parents had genotyping. PubMed:30796655

Approved on: 2019-08-28

Published on: 2020-01-24

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