Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001709.5(BDNF):āc.365T>Cā(p.Met122Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M122I) has been classified as Uncertain significance.
BDNF (HGNC:1033): (brain derived neurotrophic factor) This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015]
Uncertain significance, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
Jul 23, 2023
The BDNF c.611T>C variant is predicted to result in the amino acid substitution p.Met204Thr. This variant has been reported in the homozygous state in an individual with intellectual disability (Harripaul et al. 2017. PubMed ID: 28397838). This variant is reported in 0.095% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-27679747-A-G). 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. -
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