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GeneBe

11-27657922-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2_SupportingPP3_Moderate

The NM_001709.5(BDNF):c.643G>A(p.Val215Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BDNF
NM_001709.5 missense

Scores

12
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.643G>A p.Val215Met missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.306-319C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.643G>A p.Val215Met missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.380-319C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022BDNF: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.33
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Pathogenic
0.97
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.91
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Pathogenic
3.0
M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.4
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Pathogenic
0.71
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Vest4
0.76
MutPred
0.88
Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);.;Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);.;Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);Loss of catalytic residue at V215 (P = 0.0173);.;
MVP
0.93
MPC
1.6
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.75
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27679469; COSMIC: COSV59233194; API