VCV000800881.7 - ClinVar

NM_000123.4(ERCC5):c.2427del (p.Asp809fs)

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.

(5)

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/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000123.4(ERCC5):c.2427del (p.Asp809fs)

Variation ID: 800881 Accession: VCV000800881.7

Type and length

Deletion, 1 bp

Location

Cytogenetic: 13q33.1 13: 102866739 (GRCh38) [ NCBI UCSC ] 13: 103519089 (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	Jan 4, 2020	Apr 6, 2024	Mar 26, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000123.4:c.2427del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000114.3:p.Asp809fs	frameshift
NM_000123.3:c.2427delT	NP_000114.2:p.Asp809Glufs	frameshift
NM_001204425.2:c.3789del	NP_001191354.2:p.Asp1263fs	frameshift
NC_000013.11:g.102866739del
NC_000013.10:g.103519089del
NG_007146.1:g.25916del
NG_086332.1:g.1152del
LRG_464:g.25916del
LRG_464t1:c.2427del

... more HGVS ... less HGVS

Protein change

D1263fs, D809fs

Other names

Canonical SPDI

NC_000013.11:102866738:T:

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.

The Genome Aggregation Database (gnomAD), exomes 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

Links

dbSNP: rs777455688 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.
BIVM-ERCC5	-	-	-	GRCh38 GRCh37	-	539
ERCC5		-	-	GRCh38 GRCh37	2	533
LOC126861834	-	-	-	GRCh38	-	96

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.
Cerebrooculofacioskeletal syndrome 3	Pathogenic (2)	criteria provided, single submitter	-	RCV000985070.2
Xeroderma pigmentosum	Likely pathogenic (1)	criteria provided, single submitter	Sep 20, 2021	RCV001732003.1
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Mar 26, 2024	RCV001784482.5

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.
Likely pathogenic (Sep 20, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Xeroderma pigmentosum Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001983398.1 First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021	Publications: PubMed (1) PubMed: 31130284 Comment: Variant summary: ERCC5 c.2427delT (p.Asp809GlufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more) Variant summary: ERCC5 c.2427delT (p.Asp809GlufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251414 control chromosomes. c.2427delT has been reported in the literature in one individual with severe fetal presentation (Monies_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cerebrooculofacioskeletal syndrome 3 Affected status: yes Allele origin: germline	Pathology and Clinical Laboratory Medicine, King Fahad Medical City Accession: SCV002073828.1 First in ClinVar: Feb 10, 2022 Last updated: Feb 10, 2022	Number of individuals with the variant: 2 Ethnicity/Population group: Arab Geographic origin: Middle East
Pathogenic (Mar 16, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: yes Allele origin: germline	AiLife Diagnostics, AiLife Diagnostics Accession: SCV002502238.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Publications: PubMed (1) PubMed: 31130284 Number of individuals with the variant: 1 Secondary finding: no
Pathogenic (Mar 26, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center Accession: SCV004806580.1 First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024
Likely pathogenic (Sep 26, 2019)	no assertion criteria provided Method: clinical testing	Cerebrooculofacioskeletal syndrome 3 Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001133018.1 First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020

Comment:

Variant summary: ERCC5 c.2427delT (p.Asp809GlufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251414 control chromosomes. c.2427delT has been reported in the literature in one individual with severe fetal presentation (Monies_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Title	Author	Journal	Year	Link
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.	Monies D	American journal of human genetics	2019	PMID: 31130284

Text-mined citations for rs777455688 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_000123.4(ERCC5):c.2427del (p.Asp809fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs777455688 ...