Submissions for variant NM_020937.4(FANCM):c.2859A>C (p.Lys953Asn)

gnomAD frequency: 0.00064  dbSNP: rs142864437

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000271250	SCV000547799	likely benign	Fanconi anemia	2024-01-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585067	SCV000692786	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	FANCM: BP4
Fulgent Genetics, Fulgent Genetics	RCV000763932	SCV000894876	uncertain significance	Spermatogenic failure 28; Premature ovarian failure 15	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000585067	SCV001790501	uncertain significance	not provided	2023-08-28	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast, ovarian, colon, and other cancers (Ballinger et al., 2016; Broderick et al., 2017; Chandrasekharappa et al., 2017; Dicks et al., 2017; Nguyen-Dumont et al., 2018; Velzquez et al., 2020; Bhai et al., 2021); This variant is associated with the following publications: (PMID: 27713038, 28678401, 29351780, 28881617, 27498913, 35495172, 32522261, 34326862)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000585067	SCV002011489	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820928	SCV002067565	uncertain significance	not specified	2020-04-22	criteria provided, single submitter	clinical testing	DNA sequence analysis of the FANCM gene demonstrated a sequence change, c.2859A>C, in exon 14 that results in an amino acid change, p.Lys953Asn. This sequence change does not appear to have been previously described in patients with FANCM-related disorders and has been described in the gnomAD database with a low population frequency of 0.19% in the non-Finnish European subpopulation (dbSNP rs142864437). The p.Lys953Asn change affects a poorly conserved amino acid residue located in a domain of the FANCM protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Lys953Asn substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Lys953Asn change remains unknown at this time.
Baylor Genetics	RCV001770252	SCV002096985	uncertain significance	Spermatogenic failure 28	2022-01-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4	RCV002255362	SCV002527341	likely benign	Hereditary cancer-predisposing syndrome	2021-03-14	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000585067	SCV004218751	likely benign	not provided	2023-03-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003897723	SCV004723749	likely benign	FANCM-related condition	2023-11-29	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Molecular Oncology - Human Genetics Lab, University of Sao Paulo	RCV001843509	SCV002103115	uncertain significance	Hepatoblastoma		no assertion criteria provided	research