VCV003328168.1 - ClinVar

NM_000546.6(TP53):c.823dup (p.Cys275fs)

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.

(1)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000546.6(TP53):c.823dup (p.Cys275fs)

Variation ID: 3328168 Accession: VCV003328168.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 17p13.1 17: 7673796-7673797 (GRCh38) [ NCBI UCSC ] 17: 7577114-7577115 (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	Aug 11, 2024	Aug 11, 2024	Apr 23, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000546.6:c.823dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000537.3:p.Cys275fs	frameshift
NM_001126112.3:c.823dup	NP_001119584.1:p.Cys275fs	frameshift
NM_001126113.3:c.823dup	NP_001119585.1:p.Cys275fs	frameshift
NM_001126114.3:c.823dup	NP_001119586.1:p.Cys275fs	frameshift
NM_001126115.2:c.427dup	NP_001119587.1:p.Cys143fs	frameshift
NM_001126116.2:c.427dup	NP_001119588.1:p.Cys143fs	frameshift
NM_001126117.2:c.427dup	NP_001119589.1:p.Cys143fs	frameshift
NM_001126118.2:c.706dup	NP_001119590.1:p.Cys236fs	frameshift
NM_001276695.3:c.706dup	NP_001263624.1:p.Cys236fs	frameshift
NM_001276696.3:c.706dup	NP_001263625.1:p.Cys236fs	frameshift
NM_001276697.3:c.346dup	NP_001263626.1:p.Cys116fs	frameshift
NM_001276698.3:c.346dup	NP_001263627.1:p.Cys116fs	frameshift
NM_001276699.3:c.346dup	NP_001263628.1:p.Cys116fs	frameshift
NM_001276760.3:c.706dup	NP_001263689.1:p.Cys236fs	frameshift
NM_001276761.3:c.706dup	NP_001263690.1:p.Cys236fs	frameshift
NM_001407262.1:c.823dup	NP_001394191.1:p.Cys275fs	frameshift
NM_001407263.1:c.706dup	NP_001394192.1:p.Cys236fs	frameshift
NM_001407264.1:c.823dup	NP_001394193.1:p.Cys275fs	frameshift
NM_001407265.1:c.706dup	NP_001394194.1:p.Cys236fs	frameshift
NM_001407266.1:c.823dup	NP_001394195.1:p.Cys275fs	frameshift
NM_001407267.1:c.706dup	NP_001394196.1:p.Cys236fs	frameshift
NM_001407268.1:c.823dup	NP_001394197.1:p.Cys275fs	frameshift
NM_001407269.1:c.706dup	NP_001394198.1:p.Cys236fs	frameshift
NM_001407270.1:c.823dup	NP_001394199.1:p.Cys275fs	frameshift
NM_001407271.1:c.706dup	NP_001394200.1:p.Cys236fs	frameshift
NR_176326.1:n.852dup		non-coding transcript variant
NC_000017.11:g.7673799dup
NC_000017.10:g.7577117dup
NG_017013.2:g.18754dup
LRG_321:g.18754dup
LRG_321t1:c.821dup	LRG_321p1:p.Cys275Leufs
LRG_321t2:c.821dup	LRG_321:p.Cys275Leufs
LRG_321t3:c.821dup	LRG_321p3:p.Cys275Leufs
LRG_321t4:c.821dup	LRG_321p4:p.Cys275Leufs
LRG_321t5:c.425dup	LRG_321p5:p.Cys143Leufs
LRG_321t6:c.425dup	LRG_321p6:p.Cys143Leufs
LRG_321t7:c.425dup	LRG_321p7:p.Cys143Leufs
LRG_321t8:c.704dup	LRG_321p8:p.Cys236Leufs

... more HGVS ... less HGVS

Protein change

C116fs, C143fs, C236fs, C275fs

Other names

Canonical SPDI

NC_000017.11:7673796:AAA:AAAA

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	3373	3472

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)	criteria provided, single submitter	Apr 23, 2024	RCV004677202.1

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 (Apr 23, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV005177942.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Comment: The c.823dupT pathogenic mutation, located in coding exon 7 of the TP53 gene, results from a duplication of T at nucleotide position 823, causing a … (more) The c.823dupT pathogenic mutation, located in coding exon 7 of the TP53 gene, results from a duplication of T at nucleotide position 823, causing a translational frameshift with a predicted alternate stop codon (p.C275Lfs*31). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)

Comment:

The c.823dupT pathogenic mutation, located in coding exon 7 of the TP53 gene, results from a duplication of T at nucleotide position 823, causing a translational frameshift with a predicted alternate stop codon (p.C275Lfs*31). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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 Aug 11, 2024

ClinVar Genomic variation as it relates to human health

NM_000546.6(TP53):c.823dup (p.Cys275fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...