Submissions for variant NM_012082.4(ZFPM2):c.2107A>C (p.Met703Leu)

gnomAD frequency: 0.00019  dbSNP: rs121908603

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000861889	SCV001002303	benign	46,XY sex reversal 9	2024-12-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330385	SCV004038179	likely benign	not specified	2023-08-19	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001529320	SCV005267899	benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005394128	SCV006056140	uncertain significance	Diaphragmatic hernia 3; Tetralogy of Fallot; 46,XY sex reversal 9	2022-09-06	criteria provided, single submitter	research
OMIM	RCV000006504	SCV000026687	pathogenic	Diaphragmatic hernia 3	2012-11-01	no assertion criteria provided	literature only
OMIM	RCV000032715	SCV000056479	pathogenic	Double outlet right ventricle	2012-11-01	no assertion criteria provided	literature only
Reproductive Health Research and Development, BGI Genomics	RCV000006504	SCV001142392	uncertain significance	Diaphragmatic hernia 3	2020-01-06	no assertion criteria provided	curation	ZFPM2 is also known as FOG2. NM_012082.3:c.2107A>C in the ZFPM2 gene has an allele frequency of 0.007 in East Asian subpopulation in the gnomAD database. Pathogenic computational verdict because pathogenic predictions from DANN, EIGEN, FATHMM-MKL, MutationTaster and PrimateAI. We interpret it as variant of uncertain significance (VUS). This variant was reported in a patient with a left-sided Congenital diaphragmatic hernia (PMID: 17568391). Tan et al reported that a patient with double outlet right ventricle harbors c.2107A>C and proven to be de novo (PMID: 21919901). Taken together, we interprete this variant as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PM6; PP3.
Reproductive Development, Murdoch Childrens Research Institute	RCV001007705	SCV001146902	benign	46,XY sex reversal 3	2019-08-26	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529320	SCV001742563	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529320	SCV001968542	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003914814	SCV004734331	likely benign	ZFPM2-related disorder	2021-03-20	no assertion criteria provided	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).