5-60605784-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018369.3(DEPDC1B):​c.971G>A​(p.Arg324Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEPDC1BNM_018369.3 linkc.971G>A p.Arg324Lys missense_variant Exon 8 of 11 ENST00000265036.10 NP_060839.2 Q8WUY9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEPDC1BENST00000265036.10 linkc.971G>A p.Arg324Lys missense_variant Exon 8 of 11 1 NM_018369.3 ENSP00000265036.5 Q8WUY9-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250600
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135442
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:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461362
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.971G>A (p.R324K) alteration is located in exon 8 (coding exon 8) of the DEPDC1B gene. This alteration results from a G to A substitution at nucleotide position 971, causing the arginine (R) at amino acid position 324 to be replaced by a lysine (K). 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
Pathogenic
0.79
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Pathogenic
0.96
D
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Pathogenic
0.82
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.038
D;D
Polyphen
1.0
D;.
Vest4
0.81
MutPred
0.61
Gain of methylation at R324 (P = 0.0061);Gain of methylation at R324 (P = 0.0061);
MVP
0.95
MPC
0.69
ClinPred
0.92
D
GERP RS
4.5
Varity_R
0.86
gMVP
0.80

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.

Other links and lift over

dbSNP: rs777146759; hg19: chr5-59901611; API