ClinVar Genomic variation as it relates to human health
NM_000136.3(FANCC):c.584A>T (p.Asp195Val)
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.
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.
Uncertain significance(1); Benign(8); Likely benign(9)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000136.3(FANCC):c.584A>T (p.Asp195Val)
Variation ID: 134305 Accession: VCV000134305.68
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.32 9: 95150025 (GRCh38) [ NCBI UCSC ] 9: 97912307 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jun 9, 2014 May 1, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000136.3:c.584A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000127.2:p.Asp195Val missense NM_001243743.2:c.584A>T NP_001230672.1:p.Asp195Val missense NM_001243744.2:c.584A>T NP_001230673.1:p.Asp195Val missense NC_000009.12:g.95150025T>A NC_000009.11:g.97912307T>A NG_011707.1:g.172685A>T LRG_497:g.172685A>T LRG_497t1:c.584A>T Q00597:p.Asp195Val - Protein change
- D195V
- Other names
- p.D195V:GAT>GTT
- Canonical SPDI
- NC_000009.12:95150024:T:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00260 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00260
The Genome Aggregation Database (gnomAD) 0.00275
1000 Genomes Project 30x 0.00297
Exome Aggregation Consortium (ExAC) 0.00308
The Genome Aggregation Database (gnomAD), exomes 0.00313
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00315
Trans-Omics for Precision Medicine (TOPMed) 0.00317
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 | ||
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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. |
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AOPEP | - | - |
GRCh38 GRCh37 |
23 | 1344 | |
FANCC | - | - |
GRCh38 GRCh37 |
632 | 1957 |
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. |
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Benign/Likely benign (10) |
criteria provided, multiple submitters, no conflicts
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May 21, 2021 | RCV000120978.28 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Sep 21, 2018 | RCV000124962.9 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000179716.28 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV001083500.11 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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May 18, 2021 | RCV000667368.17 | |
Likely benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000988215.3 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001356570.3 |
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. |
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000302521.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539136.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband of European ancestry in homozygous state (Verlander 1994). Classified as Benign in ClinVar by GeneDx. MAF 0.4%. (less)
Method: Genome/Exome Filtration
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Likely benign
(Sep 29, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000594678.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Likely benign
(May 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000791802.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Benign
(Aug 24, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000232007.5
First in ClinVar: Jun 29, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137852.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001329919.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Uncertain significance
(May 29, 2019)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001522905.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Benign
(Oct 16, 2020)
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criteria provided, single submitter
Method: curation
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002535110.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Sep 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000673285.5
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(Dec 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Vantari Genetics
Accession: SCV000267037.1
First in ClinVar: Apr 13, 2016 Last updated: Apr 13, 2016 |
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Likely Benign
(Aug 26, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281279.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Converted during submission to Likely benign.
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Benign
(Oct 17, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000168402.11
First in ClinVar: Jun 09, 2014 Last updated: Aug 27, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001653385.1
First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021 |
Sex: mixed
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Benign
(May 21, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002047091.2
First in ClinVar: Jan 03, 2022 Last updated: Dec 31, 2022 |
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Benign
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010154.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000261219.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(Mar 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000892896.22
First in ClinVar: Mar 31, 2019 Last updated: Apr 15, 2024 |
Comment:
FANCC: BP4, BS2
Number of individuals with the variant: 28
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Benign
(Jun 14, 2017)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002081244.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001551778.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The FANCC p.Asp195Val variant was identified in 2 of 436 proband chromosomes (frequency: 0.005) from individuals or families of northern or eastern European and southern … (more)
The FANCC p.Asp195Val variant was identified in 2 of 436 proband chromosomes (frequency: 0.005) from individuals or families of northern or eastern European and southern Italian descent with pancreatic cancer and Fanconi Anemia (Verlander 1994, Van Der Heijden 2003). The variant was also identified in the following databases: dbSNP (ID: rs1800365), in the ClinVar database as benign by GeneDx, Emory Genetics, Invitae, Vantari Genetics; as likely benign by Centre for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, Prevention Genetics and Laboratory for Molecular Medicine, Partners Health Care Personalized Medicine; and as uncertain significance by Division of Genomic Diagnostics, Children's Hospital of Philadelphia Study Description: and in Clinvitae database as benign by Emyclass. The variant was also listed in the LOVD 3.0 database; however no relevant information was given. The variant was not identified in Cosmic and MutDB. In addition, the variant was identified in the 1000 Genomes Project in 13 of 5000 chromosomes (frequency: 0.003) and the NHLBI GO Exome Sequencing Project in 40 of 8600 European American and in 4 of 4406 African American alleles. The variant was identified in control databases in 842 (4 homozygous) of 277070 chromosomes at a frequency of 0.003 increasing the likelihood this could be a low frequency variant (Genome Aggregation Consortium Feb 27, 2017). Breakdown of observations by population is: European (Non-Finnish) in 568 (3 homozygous) of 126606 chromosomes (freq: 0.004), Ashkenazi Jewish in 36 of 10144 chromosomes (freq: 0.004), South Asian in 107 of 30766 chromosomes (freq: 0.003), Latino in 95 (1 homozygous) of 34412 chromosomes (freq: 0.003), Other in 16 of 6456 chromosomes (freq: 0.001), African in 12 of 24028 chromosomes (freq: 0.0005), and European (Finnish) in 8 of 25788 chromosomes (freq: 0.0003), while not observed in the East Asian population. The p.Asp195 residue is conserved in in mammals but not in more distantly related organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the p.Asp195Val variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant is located with the Fanconi anaemia group C protein functional domain. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
Number of individuals with the variant: 18
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807888.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927745.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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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: SCV001957656.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085146.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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Uncertain significance
(Jul 01, 2015)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Claim with insufficient supporting evidence
Source: ClinGen
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not specified
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000257632.2
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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Uncertain significance
(Feb 28, 2020)
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Flagged submission
flagged submission
Method: curation
Reason: Older claim that does not account for recent evidence
Source: ClinGen
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not provided
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001365302.1
First in ClinVar: Jun 29, 2020 Last updated: Jun 29, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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
HelpTitle | Author | Journal | Year | Link |
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Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
Retroviral gene transfer for the assignment of Fanconi anemia (FA) patients to a FA complementation group. | Fu KL | Human genetics | 1998 | PMID: 9521584 |
Sequence variations in the Fanconi anaemia gene, FAC: pathogenicity of 1806insA and R548X and recognition of D195V as a polymorphic variant. | Lo ten Foe JR | Human genetics | 1996 | PMID: 8882868 |
Mutation analysis of the Fanconi anemia gene FACC. | Verlander PC | American journal of human genetics | 1994 | PMID: 8128956 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FANCC | - | - | - | - |
Text-mined citations for rs1800365 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.