VCV001713235.2 - ClinVar

NM_000546.6(TP53):c.715_718dup (p.Ser240fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000546.6(TP53):c.715_718dup (p.Ser240fs)

Variation ID: 1713235 Accession: VCV001713235.2

Type and length

Duplication, 4 bp

Location

Cytogenetic: 17p13.1 17: 7674244-7674245 (GRCh38) [ NCBI UCSC ] 17: 7577562-7577563 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 2, 2023	Jul 16, 2023	Jul 3, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000546.6:c.715_718dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000537.3:p.Ser240fs	frameshift
NM_000546.6:c.715_718dupAACA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001126112.3:c.715_718dup	NP_001119584.1:p.Ser240fs	frameshift
NM_001126113.3:c.715_718dup	NP_001119585.1:p.Ser240fs	frameshift
NM_001126114.3:c.715_718dup	NP_001119586.1:p.Ser240fs	frameshift
NM_001126115.2:c.319_322dup	NP_001119587.1:p.Ser108fs	frameshift
NM_001126116.2:c.319_322dup	NP_001119588.1:p.Ser108fs	frameshift
NM_001126117.2:c.319_322dup	NP_001119589.1:p.Ser108fs	frameshift
NM_001126118.2:c.598_601dup	NP_001119590.1:p.Ser201fs	frameshift
NM_001276695.3:c.598_601dup	NP_001263624.1:p.Ser201fs	frameshift
NM_001276696.3:c.598_601dup	NP_001263625.1:p.Ser201fs	frameshift
NM_001276697.3:c.238_241dup	NP_001263626.1:p.Ser81fs	frameshift
NM_001276698.3:c.238_241dup	NP_001263627.1:p.Ser81fs	frameshift
NM_001276699.3:c.238_241dup	NP_001263628.1:p.Ser81fs	frameshift
NM_001276760.3:c.598_601dup	NP_001263689.1:p.Ser201fs	frameshift
NM_001276761.3:c.598_601dup	NP_001263690.1:p.Ser201fs	frameshift
NM_001407262.1:c.715_718dup	NP_001394191.1:p.Ser240Lysfs	frameshift
NM_001407263.1:c.598_601dup	NP_001394192.1:p.Ser201Lysfs	frameshift
NM_001407264.1:c.715_718dup	NP_001394193.1:p.Ser240Lysfs	frameshift
NM_001407265.1:c.598_601dup	NP_001394194.1:p.Ser201Lysfs	frameshift
NM_001407266.1:c.715_718dup	NP_001394195.1:p.Ser240Lysfs	frameshift
NM_001407267.1:c.598_601dup	NP_001394196.1:p.Ser201Lysfs	frameshift
NM_001407268.1:c.715_718dup	NP_001394197.1:p.Ser240Lysfs	frameshift
NM_001407269.1:c.598_601dup	NP_001394198.1:p.Ser201Lysfs	frameshift
NM_001407270.1:c.715_718dup	NP_001394199.1:p.Ser240Lysfs	frameshift
NM_001407271.1:c.598_601dup	NP_001394200.1:p.Ser201Lysfs	frameshift
NR_176326.1:n.744_747dup
NC_000017.11:g.7674245_7674248dup
NC_000017.10:g.7577563_7577566dup
NG_017013.2:g.18303_18306dup
LRG_321:g.18303_18306dup
LRG_321t1:c.715_718dup	LRG_321p1:p.Ser240Lysfs
LRG_321t2:c.715_718dup	LRG_321:p.Ser240Lysfs
LRG_321t3:c.715_718dup	LRG_321p3:p.Ser240Lysfs
LRG_321t4:c.715_718dup	LRG_321p4:p.Ser240Lysfs
LRG_321t5:c.319_322dup	LRG_321p5:p.Ser108Lysfs
LRG_321t6:c.319_322dup	LRG_321p6:p.Ser108Lysfs
LRG_321t7:c.319_322dup	LRG_321p7:p.Ser108Lysfs
LRG_321t8:c.598_601dup	LRG_321p8:p.Ser201Lysfs

... more HGVS ... less HGVS

Protein change

S108fs, S201fs, S240fs, S81fs

Other names

Canonical SPDI

NC_000017.11:7674244:TGTT:TGTTTGTT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TP53		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3367	3466

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hereditary cancer-predisposing syndrome	Pathogenic (1)	no assertion criteria provided	Aug 26, 2022	RCV003156030.1
Hereditary cancer-predisposing syndrome Li-Fraumeni syndrome	Pathogenic (1)	no assertion criteria provided	Jul 3, 2023	RCV003312050.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 26, 2022)	no assertion criteria provided Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: yes Allele origin: germline	BRCAlab, Lund University Accession: SCV002589034.1 First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Pathogenic (Jul 03, 2023)	no assertion criteria provided Method: clinical testing	Hereditary cancer-predisposing syndrome Li-Fraumeni syndrome Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breast Care Center, Daerim St. Mary`s Hospital Accession: SCV003936105.1 First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023	Comment: The TP53:c.715_718dup variant was located in coding exon 7 of the TP53 gene and resulted in a frame-shift predicted to cause NMD(nonsense-mediated decay), which is … (more) The TP53:c.715_718dup variant was located in coding exon 7 of the TP53 gene and resulted in a frame-shift predicted to cause NMD(nonsense-mediated decay), which is a known mechanism of disease. It was not found in gnomAD genomes and gnomAD exomes. This pathogenic variant was detected in a 29-year-old Korean female who had ipsilateral breast tumor (DCIS) recurrence at the ages of 19 and 29. She had a second-degree relative with leukemia. (less) Indication for testing: Breast cancer before the age of 31 years Age: 20-29 years Sex: female Ethnicity/Population group: East Asian Geographic origin: South Korea

Comment:

The TP53:c.715_718dup variant was located in coding exon 7 of the TP53 gene and resulted in a frame-shift predicted to cause NMD(nonsense-mediated decay), which is a known mechanism of disease. It was not found in gnomAD genomes and gnomAD exomes. This pathogenic variant was detected in a 29-year-old Korean female who had ipsilateral breast tumor (DCIS) recurrence at the ages of 19 and 29. She had a second-degree relative with leukemia.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000546.6(TP53):c.715_718dup (p.Ser240fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...