ClinVar Miner

Submissions for variant NM_012082.4(ZFPM2):c.89A>G (p.Glu30Gly)

gnomAD frequency: 0.00302  dbSNP: rs121908601
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000461090 SCV000557284 likely benign 46,XY sex reversal 9 2025-01-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818141 SCV002071439 likely benign not specified 2017-08-08 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001573801 SCV004032829 benign not provided 2025-03-01 criteria provided, single submitter clinical testing ZFPM2: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics RCV001573801 SCV005224033 likely benign not provided criteria provided, single submitter not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001818141 SCV005726620 benign not specified 2024-11-19 criteria provided, single submitter clinical testing Variant summary: ZFPM2 c.89A>G (p.Glu30Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0042 in 1613668 control chromosomes in the gnomAD database, including 18 homozygotes. The variant allele was found at a frequency of 0.0042 in 1613668 control chromosomes, predominantly at a frequency of 0.0052 within the Non-Finnish European subpopulation in the gnomAD database, including 15 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2500-fold of the estimated maximal expected allele frequency for a pathogenic variant in ZFPM2 causing Tetralogy Of Fallot phenotype (2.1e-06), strongly suggesting the variant is a benign polymorphism. c.89A>G has been reported in the literature in control individuals and in individuals affected with Tetralogy Of Fallot or with atrioventricular septal defect, both without evidence of causality (e.g. D'Alessandro_2018, Pizzuti_2003, Priest_2016, Freudenberg-Hua_2014). These reports do not provide unequivocal conclusions about association of the variant with Tetralogy Of Fallot. At least one publication reports experimental evidence evaluating an impact on protein function, showing no damaging effect of this variant evidenced by maintained binding with and transcriptional activity of co-regulator of transcription, GATA4 (e.g. Pizzuti_2003). The following publications have been ascertained in the context of this evaluation (PMID: 25996639, 14517948, 27058611, 25333069). ClinVar contains an entry for this variant (Variation ID: 6128). Based on the evidence outlined above, the variant was classified as benign.
OMIM RCV000006502 SCV000026685 pathogenic Tetralogy of Fallot 2015-04-01 no assertion criteria provided literature only
OMIM RCV000032713 SCV000056477 pathogenic Double outlet right ventricle 2015-04-01 no assertion criteria provided literature only
OMIM RCV000172841 SCV000223807 pathogenic Diaphragmatic hernia 3 2015-04-01 no assertion criteria provided literature only
Reproductive Development, Murdoch Childrens Research Institute RCV001007696 SCV001146893 benign 46,XY sex reversal 3 2019-08-26 no assertion criteria provided research
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573801 SCV001800183 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001573801 SCV001931789 likely benign not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003924804 SCV004739158 likely benign ZFPM2-related disorder 2021-08-16 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).

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