VCV000129013.25 - ClinVar

NM_000124.4(ERCC6):c.1196G>A (p.Gly399Asp)

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.

(17)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000124.4(ERCC6):c.1196G>A (p.Gly399Asp)

Variation ID: 129013 Accession: VCV000129013.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q11.23 10: 49524234 (GRCh38) [ NCBI UCSC ] 10: 50732280 (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	Jul 6, 2014	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000124.4:c.1196G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000115.1:p.Gly399Asp	missense
NM_001277058.2:c.1196G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001263987.1:p.Gly399Asp	missense
NM_001277059.2:c.1196G>A	NP_001263988.1:p.Gly399Asp	missense
NM_001346440.2:c.1196G>A	NP_001333369.1:p.Gly399Asp	missense
NM_170753.3:c.-209G>A		5 prime UTR
NC_000010.11:g.49524234C>T
NC_000010.10:g.50732280C>T
NG_009442.1:g.19868G>A
NG_033155.1:g.5048G>A
LRG_465:g.19868G>A
LRG_465t1:c.1196G>A	LRG_465p1:p.Gly399Asp
	Q03468:p.Gly399Asp

... more HGVS ... less HGVS

Protein change

G399D

Other names

Canonical SPDI

NC_000010.11:49524233:C: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.

0.23782 (T)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.16231

The Genome Aggregation Database (gnomAD) 0.17598

Trans-Omics for Precision Medicine (TOPMed) 0.18718

Exome Aggregation Consortium (ExAC) 0.19578

The Genome Aggregation Database (gnomAD), exomes 0.20189

1000 Genomes Project 0.23782

1000 Genomes Project 30x 0.23876

Links

ClinGen: CA152774 UniProtKB: Q03468#VAR_001217 dbSNP: rs2228528 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.
ERCC6		-	-	GRCh38 GRCh37	1580	1957
PGBD3	-	-	-	GRCh38 GRCh37	-	245

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.
not specified	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Dec 3, 2021	RCV000116994.22
Macular degeneration	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000278377.6
Cockayne syndrome	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000335722.6
COFS syndrome	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000375364.6
Cerebrooculofacioskeletal syndrome 1	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001657731.3
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001519187.10
UV-sensitive syndrome 1	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001657732.3
Cockayne syndrome type 2	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001657729.3
DE SANCTIS-CACCHIONE SYNDROME	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001657730.3

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.
Benign (Jun 11, 2012)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	Not specified (Autosomal recessive inheritance) Affected status: not provided Allele origin: germline	Claritas Genomics Accession: SCV000222779.1 First in ClinVar: May 09, 2015 Last updated: May 09, 2015
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Cerebrooculofacioskeletal Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000362944.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Cockayne Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000362946.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Macular Degeneration Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000362945.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cerebrooculofacioskeletal syndrome 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001876152.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cockayne syndrome type 2 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001876153.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	DE SANCTIS-CACCHIONE SYNDROME Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001876154.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	UV-sensitive syndrome 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001876156.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Likely benign (Dec 03, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002051101.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Benign (Nov 10, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001943554.2 First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 25026993, 20044625)
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001728012.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000302365.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jan 28, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000230846.5 First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ERCC6 Number of individuals with the variant: 1 Sex: mixed
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005220692.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001953256.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001967543.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151115.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
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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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ERCC6	-	-	-	-

Text-mined citations for rs2228528 ...

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 Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_000124.4(ERCC6):c.1196G>A (p.Gly399Asp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2228528 ...