chr11-27658560-G-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001709.5(BDNF):c.5C>A(p.Thr2Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2I) has been classified as Likely benign.
Frequency
Consequence
NM_001709.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BDNF | NM_001709.5 | c.5C>A | p.Thr2Asn | missense_variant | 2/2 | ENST00000356660.9 | |
BDNF-AS | NR_033312.1 | n.527+98G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BDNF | ENST00000356660.9 | c.5C>A | p.Thr2Asn | missense_variant | 2/2 | 1 | NM_001709.5 | P4 | |
BDNF-AS | ENST00000651238.1 | n.601+98G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 40AN: 250832Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135758
GnomAD4 exome AF: 0.000247 AC: 361AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.000261 AC XY: 190AN XY: 727234
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74350
ClinVar
Submissions by phenotype
BDNF-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 2023 | The BDNF c.251C>A variant is predicted to result in the amino acid substitution p.Thr84Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.033% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-27680107-G-T), which is higher than expected for a pathogenic variant in this gene. An alternate change at the same amino acid position was initially documented in association with central hypoventilation syndrome (p.Thr84Ile, documented in the literature on an alternate transcript – NM_001709.5 p.Thr2Ile; Weese-Mayer et al. 2002. PubMed ID: 11840487; Friedel et al. 2005. PubMed ID: 15457498). However, it has an even higher allele frequency than the p.Thr84Asn change, and its pathogenicity was called into question by multiple later reports (Abouelhoda et al. 2016. PubMed ID: 27884173; Rego et al. 2018. PubMed ID: 30487145). Although we suspect that the c.251C>A (p.Thr84Asn) 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at