Submissions for variant NM_001202.6(BMP4):c.89C>T (p.Thr30Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003069750	SCV003471804	uncertain significance	Microphthalmia with brain and digit anomalies; Orofacial cleft 11	2022-09-14	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with BMP4-related conditions. This variant is present in population databases (rs565895316, gnomAD 0.03%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 30 of the BMP4 protein (p.Thr30Met).
PreventionGenetics, part of Exact Sciences	RCV003404067	SCV004121128	uncertain significance	BMP4-related disorder	2022-12-14	criteria provided, single submitter	clinical testing	The BMP4 c.89C>T variant is predicted to result in the amino acid substitution p.Thr30Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-54418852-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.