Submissions for variant NM_000135.4(FANCA):c.3239+1dup

dbSNP: rs766989857

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000821969	SCV000962745	pathogenic	Fanconi anemia	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change affects a splice site in intron 32 of the FANCA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs766989857, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with Fanconi anemia (PMID: 21659346; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 663982). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV003448350	SCV004176364	pathogenic	Fanconi anemia complementation group A	2023-02-14	criteria provided, single submitter	clinical testing	The splice site donor variant c.3239+1dup in the FANCA gene has been observed in individual(s) with Fanconi anemia (Tsangaris, E et al., 2011). This variant is reported with the allele frequency (0.001%) in the gnomAD Exomes and novel in 1000 Genomes. This splice variant in intron 32 affects the position 1 nucleotide downstream of exon 32. It is submitted to ClinVar as Pathogenic/ Uncertain Significance. Loss-of-function variants in FANCA are known to be pathogenic (Moghrabi, Nabil N et al., 2009). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003448350	SCV004196031	pathogenic	Fanconi anemia complementation group A	2023-09-14	criteria provided, single submitter	clinical testing
Dept. of Cytogenetics, ICMR- National Institute of Immunohaematology	RCV000821969	SCV001832580	uncertain significance	Fanconi anemia		flagged submission	clinical testing
Natera, Inc.	RCV000821969	SCV002092545	pathogenic	Fanconi anemia	2021-01-19	no assertion criteria provided	clinical testing