Genetic Variant DEPDC1B:p.Asn255Ser (chr5-60638884-T-C) – 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.764A>G(p.Asn255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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=0.17568362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3 link	c.764A>G	p.Asn255Ser	missense_variant	Exon 7 of 11	ENST00000265036.10	NP_060839.2	Q8WUY9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DEPDC1B	ENST00000265036.10 link	c.764A>G	p.Asn255Ser	missense_variant	Exon 7 of 11	1	NM_018369.3	ENSP00000265036.5	Q8WUY9-1
DEPDC1B	ENST00000453022.6 link	c.764A>G	p.Asn255Ser	missense_variant	Exon 7 of 10	2		ENSP00000389101.2	Q8WUY9-2
DEPDC1B	ENST00000512078.5 link	n.*761A>G		non_coding_transcript_exon_variant	Exon 8 of 11	2		ENSP00000427527.1	D6RIB0
DEPDC1B	ENST00000512078.5 link	n.*761A>G		3_prime_UTR_variant	Exon 8 of 11	2		ENSP00000427527.1	D6RIB0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243560

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000124

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455474

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.764A>G (p.N255S) alteration is located in exon 7 (coding exon 7) of the DEPDC1B gene. This alteration results from a A to G substitution at nucleotide position 764, causing the asparagine (N) at amino acid position 255 to be replaced by a serine (S). 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

0.058

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.055

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.15

Sift

Benign

0.14

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;.

Vest4

0.14

MutPred

0.53

Gain of methylation at K260 (P = 0.1089);Gain of methylation at K260 (P = 0.1089);

MVP

0.41

MPC

0.13

ClinPred

0.056

GERP RS

3.1

Varity_R

0.045

gMVP

0.13

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