5-177458234-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001363541.2(DBN1):​c.1738G>C​(p.Asp580His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DBN1
NM_001363541.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74
Variant links:
Genes affected
DBN1 (HGNC:2695): (drebrin 1) The protein encoded by this gene is a cytoplasmic actin-binding protein thought to play a role in the process of neuronal growth. It is a member of the drebrin family of proteins that are developmentally regulated in the brain. A decrease in the amount of this protein in the brain has been implicated as a possible contributing factor in the pathogenesis of memory disturbance in Alzheimer's disease. At least two alternative splice variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2996598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DBN1NM_001363541.2 linkc.1738G>C p.Asp580His missense_variant Exon 13 of 15 ENST00000393565.6 NP_001350470.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DBN1ENST00000393565.6 linkc.1738G>C p.Asp580His missense_variant Exon 13 of 15 5 NM_001363541.2 ENSP00000377195.1 Q16643-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
76
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1606G>C (p.D536H) alteration is located in exon 13 (coding exon 12) of the DBN1 gene. This alteration results from a G to C substitution at nucleotide position 1606, causing the aspartic acid (D) at amino acid position 536 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;.;.;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.30
T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.1
L;.;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.0
N;N;N;D
REVEL
Benign
0.13
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.50
MutPred
0.19
Gain of helix (P = 0.132);.;.;.;
MVP
0.67
MPC
0.64
ClinPred
0.90
D
GERP RS
4.6
Varity_R
0.39
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr5-176885235; API