Genetic Variant NM_018369.3:c.1085G>A (chr5-60603548-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018369.3(DEPDC1B):c.1085G>A(p.Arg362His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,602,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.390

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1387012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3 link	c.1085G>A	p.Arg362His	missense_variant	Exon 9 of 11	ENST00000265036.10	NP_060839.2	Q8WUY9-1
DEPDC1B	NM_001145208.2 link	c.1085G>A	p.Arg362His	missense_variant	Exon 9 of 10		NP_001138680.1	Q8WUY9-2
DEPDC1B	XM_011543509.3 link	c.1040G>A	p.Arg347His	missense_variant	Exon 9 of 11		XP_011541811.1
DEPDC1B	XM_047417369.1 link	c.1040G>A	p.Arg347His	missense_variant	Exon 9 of 10		XP_047273325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DEPDC1B	ENST00000265036.10 link	c.1085G>A	p.Arg362His	missense_variant	Exon 9 of 11	1	NM_018369.3	ENSP00000265036.5	Q8WUY9-1
DEPDC1B	ENST00000453022.6 link	c.1085G>A	p.Arg362His	missense_variant	Exon 9 of 10	2		ENSP00000389101.2	Q8WUY9-2
DEPDC1B	ENST00000512078.5 link	n.*1082G>A		non_coding_transcript_exon_variant	Exon 10 of 11	2		ENSP00000427527.1	D6RIB0
DEPDC1B	ENST00000512078.5 link	n.*1082G>A		3_prime_UTR_variant	Exon 10 of 11	2		ENSP00000427527.1	D6RIB0

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000293

AC:

AN:

239058

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

129182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000547

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1450744

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

721448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000284

Hom.:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085G>A (p.R362H) alteration is located in exon 9 (coding exon 9) of the DEPDC1B gene. This alteration results from a G to A substitution at nucleotide position 1085, causing the arginine (R) at amino acid position 362 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

0.075

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.067

Sift

Benign

0.14

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0020

B;.

Vest4

0.17

MutPred

0.75

Gain of catalytic residue at C363 (P = 0.0608);Gain of catalytic residue at C363 (P = 0.0608);

MVP

0.37

MPC

0.21

ClinPred

0.16

GERP RS

0.28

Varity_R

0.051

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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