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11-27658008-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2_SupportingPP3_StrongPP5_Moderate

The NM_001709.5(BDNF):c.557G>A(p.Cys186Tyr) 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 Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BDNF
NM_001709.5 missense

Scores

13
3
2

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.91

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.979
PP5
?
Variant 11-27658008-C-T is Pathogenic according to our data. Variant chr11-27658008-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 981928.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.557G>A p.Cys186Tyr missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.306-233C>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.557G>A p.Cys186Tyr missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.380-233C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Obesity Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingInstitute of Human Genetics, University of GoettingenOct 13, 2020ACMG criteria used for classification: PS2, PM2, PP3, BP1. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
Cadd
Pathogenic
26
Dann
Benign
0.97
DEOGEN2
Uncertain
0.65
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.62
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
0.94
D
PROVEAN
Pathogenic
-10
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
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
0.96
MutPred
0.90
Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);.;Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);.;Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);Loss of methylation at K185 (P = 0.0306);.;
MVP
0.94
MPC
2.1
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.95
gMVP
1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1852795747; hg19: chr11-27679555; API