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Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).

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Criteria Specification: CSpec Registry PDF

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

CA397836247

633606 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance

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

Met criteria codes 3
PVS1_Strong PM6_Supporting PM2_Supporting
Unmet criteria codes 2
PS2 PS4

Expert Panel

Evidence Links 1

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.
Met criteria codes
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
PM2_Supporting
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Unmet criteria codes
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.

Approved on: 2019-08-28
Published on: 2020-01-24
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