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]

Variant: NM_001126112.2(TP53):c.673-5C>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10580927

230648 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c5369d36-5474-4593-bd76-319092423c63

Approved on: 2021-09-24

Published on: 2021-09-24

HGVS expressions

NM_001126112.2:c.673-5C>G

NM_001126112.2(TP53):c.673-5C>G

ENST00000269305.9:c.673-5C>G

ENST00000269305.8:c.673-5C>G

ENST00000359597.8:n.673-5C>G

ENST00000413465.6:n.673-5C>G

ENST00000420246.6:c.673-5C>G

ENST00000445888.6:c.673-5C>G

ENST00000455263.6:c.673-5C>G

ENST00000504290.5:c.277-5C>G

ENST00000504937.5:c.277-5C>G

ENST00000509690.5:c.277-5C>G

ENST00000510385.5:c.277-5C>G

ENST00000514944.5:c.394-5C>G

ENST00000574684.1:n.68-5C>G

ENST00000610292.4:c.556-5C>G

ENST00000610538.4:c.556-5C>G

ENST00000610623.4:c.196-5C>G

ENST00000615910.4:n.640-5C>G

ENST00000617185.4:c.673-5C>G

ENST00000618944.4:c.196-5C>G

ENST00000619186.4:c.196-5C>G

ENST00000619485.4:c.556-5C>G

ENST00000620739.4:c.556-5C>G

ENST00000622645.4:c.556-5C>G

ENST00000635293.1:c.556-5C>G

NM_000546.5:c.673-5C>G

NM_001126113.2:c.673-5C>G

NM_001126114.2:c.673-5C>G

NM_001126115.1:c.277-5C>G

NM_001126116.1:c.277-5C>G

NM_001126117.1:c.277-5C>G

NM_001126118.1:c.556-5C>G

NM_001276695.1:c.556-5C>G

NM_001276696.1:c.556-5C>G

NM_001276697.1:c.196-5C>G

NM_001276698.1:c.196-5C>G

NM_001276699.1:c.196-5C>G

NM_001276760.1:c.556-5C>G

NM_001276761.1:c.556-5C>G

NM_001276695.2:c.556-5C>G

NM_001276696.2:c.556-5C>G

NM_001276697.2:c.196-5C>G

NM_001276698.2:c.196-5C>G

NM_001276699.2:c.196-5C>G

NM_001276760.2:c.556-5C>G

NM_001276761.2:c.556-5C>G

NM_000546.6:c.673-5C>G

NM_001126112.3:c.673-5C>G

NM_001126113.3:c.673-5C>G

NM_001126114.3:c.673-5C>G

NM_001126115.2:c.277-5C>G

NM_001126116.2:c.277-5C>G

NM_001126117.2:c.277-5C>G

NM_001126118.2:c.556-5C>G

NM_001276695.3:c.556-5C>G

NM_001276696.3:c.556-5C>G

NM_001276697.3:c.196-5C>G

NM_001276698.3:c.196-5C>G

NM_001276699.3:c.196-5C>G

NM_001276760.3:c.556-5C>G

NM_001276761.3:c.556-5C>G

NC_000017.11:g.7674295G>C

CM000679.2:g.7674295G>C

NC_000017.10:g.7577613G>C

CM000679.1:g.7577613G>C

NC_000017.9:g.7518338G>C

NG_017013.2:g.18256C>G

Likely Benign

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

PM2_Supporting BS2_Supporting BP4

PS2 PS1 PS4 PS3 PP1 PP3 PM6 PM5 PM1 BA1 BS4 BS3 BS1 BP2 PVS1

Evidence Links 1

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). The SpliceAI splice site predictor indicates that the variant has no impact on splicing (BP4). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; Invitae). In summary, TP53 c.673-5C>G 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, BP4, BS2_Supporting.

PM2_Supporting

Absent from gnomAD non-cancer.

BS2_Supporting

Not seen in FLOSSIES. Seen in 4 cancer-free women 60+ at Invitae and once at GeneDx.

BP4

Intronic variant with no splice impact predicted. (VarSeak Class 2; SpliceAI <0.2)

PS2

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

PS1

Intronic

PS4

Seen 18 times across 4 laboratories; no criteria met. Not found as a germline variant in the literature.

PS3

None found for this variant.

This describes the splice variant at c.673-2A which appears to affect ability to bind DNA. NOT the variant in question. PubMed:25074920

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

PM6

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

PM5

Intronic

PM1

Not in cancerhotspots.com

BA1

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

BS4

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

BS3

None found for this variant.

This describes the splice variant at c.673-2A which appears to affect ability to bind DNA. NOT the variant in question. PubMed:25074920

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

PVS1

Intronic variant; not at canonical splice site

Curation History

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