Submissions for variant NM_007055.3(POLR3A):c.2554A>G (rs267608671)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413750	SCV000491315	likely pathogenic	not provided	2016-03-12	criteria provided, single submitter	clinical testing	The M852V variant in the POLR3A gene has been reported previously in several individuals with leukodystrophy, hypogonadotropic hypogonadism, and dental anomalies (Bernard et al., 2011; Terao et al., 2012; Daoud et al., 2013; Wolf et al., 2014). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common variant in these populations. The M852V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The M852V variant is a strong candidate for a pathogenic variant.
OMIM	RCV000024141	SCV000045432	pathogenic	Hypomyelinating leukodystrophy 7	2011-09-09	no assertion criteria provided	literature only
GeneReviews	RCV000024141	SCV000055886	pathologic	Hypomyelinating leukodystrophy 7	2012-08-02	no assertion criteria provided	curation	Converted during submission to Pathogenic.