chr5-177458587-C-T

Variant names:

• chr5-177458587-C-T
• rs1756749566
• NM_001363541.2:c.1385G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363541.2(DBN1):​c.1385G>A​(p.Ser462Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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: 2.99
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116832614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363541.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBN1	NM_001363541.2	MANE Select	c.1385G>A	p.Ser462Asn	missense	Exon 13 of 15	NP_001350470.2	Q16643-3
	DBN1	NM_001393630.1		c.1391G>A	p.Ser464Asn	missense	Exon 14 of 16	NP_001380559.1
	DBN1	NM_001364151.2		c.1382G>A	p.Ser461Asn	missense	Exon 13 of 15	NP_001351080.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBN1	ENST00000393565.6	TSL:5 MANE Select	c.1385G>A	p.Ser462Asn	missense	Exon 13 of 15	ENSP00000377195.1	Q16643-3
	DBN1	ENST00000292385.9	TSL:1	c.1253G>A	p.Ser418Asn	missense	Exon 13 of 15	ENSP00000292385.5	Q16643-2
	DBN1	ENST00000309007.9	TSL:1	c.1247G>A	p.Ser416Asn	missense	Exon 12 of 14	ENSP00000308532.5	Q16643-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.78
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.095
Sift	Benign	0.30	T
Sift4G	Benign	0.23	T
Polyphen		0.12	B
Vest4		0.16
MutPred		0.20		Loss of glycosylation at S416 (P = 0.009)
MVP		0.40
MPC		0.12
ClinPred		0.16	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.092
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1756749566; hg19: chr5-176885588;