VCV000134258.13 - ClinVar

NM_000135.4(FANCA):c.2567T>C (p.Leu856Ser)

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.

(6)

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.

Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000135.4(FANCA):c.2567T>C (p.Leu856Ser)

Variation ID: 134258 Accession: VCV000134258.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q24.3 16: 89767175 (GRCh38) [ NCBI UCSC ] 16: 89833583 (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	Jun 9, 2014	Feb 28, 2024	Dec 19, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000135.4:c.2567T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000126.2:p.Leu856Ser	missense
NM_001286167.3:c.2567T>C	NP_001273096.1:p.Leu856Ser	missense
NC_000016.10:g.89767175A>G
NC_000016.9:g.89833583A>G
NG_011706.1:g.54483T>C
LRG_495:g.54483T>C
LRG_495t1:c.2567T>C

... more HGVS ... less HGVS

Protein change

L856S

Other names

Canonical SPDI

NC_000016.10:89767174:A:G

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.

0.00020 (G)

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

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD) 0.00004

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

The Genome Aggregation Database (gnomAD), exomes 0.00008

Exome Aggregation Consortium (ExAC) 0.00012

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA159284 dbSNP: rs370085403 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.
FANCA		-	-	GRCh38 GRCh37	4167	5325

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	not provided (1)	no classification provided	Sep 19, 2013	RCV000120931.2
Fanconi anemia complementation group A	Uncertain significance (2)	criteria provided, single submitter	Jul 19, 2017	RCV000668295.2
not provided	Uncertain significance (1)	criteria provided, single submitter	Jan 23, 2020	RCV000766439.3
Fanconi anemia	Likely benign (1)	criteria provided, single submitter	Dec 19, 2023	RCV001447411.7
FANCA-related disorder	Uncertain significance (1)	criteria provided, single submitter	Jul 21, 2023	RCV003398726.4

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.
Uncertain significance (Jan 23, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000573677.6 First in ClinVar: Jun 09, 2014 Last updated: Mar 04, 2023	Comment: In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24728327)
Likely benign (Dec 19, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Fanconi anemia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001650475.4 First in ClinVar: May 23, 2021 Last updated: Feb 28, 2024
Uncertain significance (Jul 19, 2017)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Fanconi anemia complementation group A Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000792869.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Uncertain significance (Jul 21, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	FANCA-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004118977.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The FANCA c.2567T>C variant is predicted to result in the amino acid substitution p.Leu856Ser. This variant has been detected by whole genome sequencing in a … (more) The FANCA c.2567T>C variant is predicted to result in the amino acid substitution p.Leu856Ser. This variant has been detected by whole genome sequencing in a healthy cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-89833583-A-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
Uncertain significance (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Fanconi anemia, group A Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001452863.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000085099.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 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

Comment:

The FANCA c.2567T>C variant is predicted to result in the amino acid substitution p.Leu856Ser. This variant has been detected by whole genome sequencing in a healthy cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-89833583-A-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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 rs370085403 ...

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 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000135.4(FANCA):c.2567T>C (p.Leu856Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs370085403 ...