Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000461090 | SCV000557284 | likely benign | 46,XY sex reversal 9 | 2025-01-14 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818141 | SCV002071439 | likely benign | not specified | 2017-08-08 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001573801 | SCV004032829 | benign | not provided | 2025-03-01 | criteria provided, single submitter | clinical testing | ZFPM2: BP4, BS1, BS2 |
Breakthrough Genomics, |
RCV001573801 | SCV005224033 | likely benign | not provided | criteria provided, single submitter | not provided | ||
Women's Health and Genetics/Laboratory Corporation of America, |
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, |
RCV001007696 | SCV001146893 | benign | 46,XY sex reversal 3 | 2019-08-26 | no assertion criteria provided | research | |
Laboratory of Diagnostic Genome Analysis, |
RCV001573801 | SCV001800183 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001573801 | SCV001931789 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
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). |