5-177458234-C-G

Variant names:

• chr5-177458234-C-G
• NM_001363541.2:c.1738G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74

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]

ACMG classification

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
DBN1	NM_001363541.2	c.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
DBN1	ENST00000393565.6	c.1738G>C	p.Asp580His	missense_variant	Exon 13 of 15	5	NM_001363541.2	ENSP00000377195.1

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

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;