Genetic Variant DEPDC1B:p.Arg488Gln (chr5-60597880-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018369.3(DEPDC1B):c.1463G>A(p.Arg488Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,611,462 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

Variant links:

Genes affected

DEPDC1B (HGNC:24902): (DEP domain containing 1B) Predicted to enable GTPase activator activity. Involved in cell migration and positive regulation of Wnt signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3 link	c.1463G>A	p.Arg488Gln	missense_variant	Exon 11 of 11	ENST00000265036.10	NP_060839.2	Q8WUY9-1
DEPDC1B	NM_001145208.2 link	c.1277G>A	p.Arg426Gln	missense_variant	Exon 10 of 10		NP_001138680.1	Q8WUY9-2
DEPDC1B	XM_011543509.3 link	c.1418G>A	p.Arg473Gln	missense_variant	Exon 11 of 11		XP_011541811.1
DEPDC1B	XM_047417369.1 link	c.1232G>A	p.Arg411Gln	missense_variant	Exon 10 of 10		XP_047273325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DEPDC1B	ENST00000265036.10 link	c.1463G>A	p.Arg488Gln	missense_variant	Exon 11 of 11	1	NM_018369.3	ENSP00000265036.5	Q8WUY9-1
DEPDC1B	ENST00000453022.6 link	c.1277G>A	p.Arg426Gln	missense_variant	Exon 10 of 10	2		ENSP00000389101.2	Q8WUY9-2
DEPDC1B	ENST00000512078.5 link	n.*1274G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000427527.1	D6RIB0
DEPDC1B	ENST00000512078.5 link	n.*1274G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000427527.1	D6RIB0

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000724

AC:

AN:

248634

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134510

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1459516

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000132

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.000363

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1463G>A (p.R488Q) alteration is located in exon 11 (coding exon 11) of the DEPDC1B gene. This alteration results from a G to A substitution at nucleotide position 1463, causing the arginine (R) at amino acid position 488 to be replaced by a glutamine (Q). 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

0.32

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.014

D;T

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;.

Vest4

0.73

MVP

0.92

MPC

0.71

ClinPred

0.72

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over