Submissions for variant NM_000135.4(FANCA):c.1115_1118del (p.Val372fs)

dbSNP: rs397507552

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000463426	SCV000547753	pathogenic	Fanconi anemia	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val372Alafs*42) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs397507552, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 8896564, 15643609, 17924555, 19367192, 21273304, 24584348). This variant is also known as 1159-1162delTTGG. ClinVar contains an entry for this variant (Variation ID: 3440). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago	RCV000003609	SCV000594661	pathogenic	Fanconi anemia complementation group A	2015-09-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001091063	SCV001246907	pathogenic	not provided	2020-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001091063	SCV002032553	pathogenic	not provided	2023-05-25	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in the heterozygous state in a patient with bone marrow failure syndrome (Perez Botero et al., 2018); This variant is associated with the following publications: (PMID: 31970404, 8896564, 29625052, 26689913, 31589614, 33630411, 33736979, 28104920, 35512711, 34308104, 33718801, 28485484)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000003609	SCV002768358	pathogenic	Fanconi anemia complementation group A	2020-05-21	criteria provided, single submitter	clinical testing	A heterozygous deletion variant was identified, NM_000135.2(FANCA):c.1115_1118del in exon 13 of 43 of the FANCA gene. (NB: This variant is non-coding in alternative transcripts). This deletion is predicted to cause a frameshift from amino acid position 372 introducing a stop codon downstream; NP_000126.2(FANCA):p.(Val372Alafs*42), resulting in loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a global population frequency of 0.0067% (19 heterozygotes, 0 homozygotes) with a European sub-population frequency of 0.014%. The variant has been previously reported in patients with Fanconi anemia (ClinVar, Pilonetto, D. V. et al. (2017), Castella, M. et al. (2011)). Other variants predicted to cause NMD have also been reported as pathogenic in individuals with Fanconi anemia (ClinVar). Based on information available at the time of curation, this variant has been classified as PATHOGENIC.
Fulgent Genetics, Fulgent Genetics	RCV000003609	SCV002781974	pathogenic	Fanconi anemia complementation group A	2022-05-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000003609	SCV003835075	pathogenic	Fanconi anemia complementation group A	2024-03-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001091063	SCV004026680	pathogenic	not provided	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001091063	SCV004221907	pathogenic	not provided	2022-05-10	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the FANCA mRNA and causes the premature termination of FANCA protein synthesis. The frequency of this variant in the general population, 0.0002 (10/50810 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in patients affected with fanconi anemia (PMIDs: 24584348 (2014), 22778927 (2012), 21273304 (2011), 19367192 (2009), 17924555 (2008), 15643609 (2005)). Based on the available information, this variant is classified as pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000003609	SCV005016472	pathogenic	Fanconi anemia complementation group A	2024-04-16	criteria provided, single submitter	clinical testing	This variant was observed in trans position to a pathogenic complex structural variant of the chromosome 16 inhertied from the mother.
Molecular Genetics and NGS Laboratory, Hospital Fundacion Valle Del Lili	RCV000003609	SCV005205558	pathogenic	Fanconi anemia complementation group A	2024-08-27	criteria provided, single submitter	clinical testing
OMIM	RCV000003609	SCV000023767	pathogenic	Fanconi anemia complementation group A	1996-11-01	no assertion criteria provided	literature only
GeneReviews	RCV000003609	SCV000057803	not provided	Fanconi anemia complementation group A		no assertion provided	literature only	Common in northern Europeans
Counsyl	RCV000003609	SCV000485663	pathogenic	Fanconi anemia complementation group A	2016-08-16	no assertion criteria provided	clinical testing
Leiden Open Variation Database	RCV000003609	SCV001425645	pathogenic	Fanconi anemia complementation group A	2020-02-28	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Daniela Pilonetto, Johan de Winter, Sue Richards.
Natera, Inc.	RCV000003609	SCV001457963	pathogenic	Fanconi anemia complementation group A	2020-09-16	no assertion criteria provided	clinical testing