dbSNP rs760880988: DEPDC1B:p.Arg362Leu (chr5-60603548-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018369.3(DEPDC1B):c.1085G>T(p.Arg362Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,748 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R362H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3 link	c.1085G>T	p.Arg362Leu	missense_variant	Exon 9 of 11	ENST00000265036.10	NP_060839.2	Q8WUY9-1
DEPDC1B	NM_001145208.2 link	c.1085G>T	p.Arg362Leu	missense_variant	Exon 9 of 10		NP_001138680.1	Q8WUY9-2
DEPDC1B	XM_011543509.3 link	c.1040G>T	p.Arg347Leu	missense_variant	Exon 9 of 11		XP_011541811.1
DEPDC1B	XM_047417369.1 link	c.1040G>T	p.Arg347Leu	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>T	p.Arg362Leu	missense_variant	Exon 9 of 11	1	NM_018369.3	ENSP00000265036.5	Q8WUY9-1
DEPDC1B	ENST00000453022.6 link	c.1085G>T	p.Arg362Leu	missense_variant	Exon 9 of 10	2		ENSP00000389101.2	Q8WUY9-2
DEPDC1B	ENST00000512078.5 link	n.*1082G>T		non_coding_transcript_exon_variant	Exon 10 of 11	2		ENSP00000427527.1	D6RIB0
DEPDC1B	ENST00000512078.5 link	n.*1082G>T		3_prime_UTR_variant	Exon 10 of 11	2		ENSP00000427527.1	D6RIB0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239058

Hom.:

AF XY:

0.00000774

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:

0.0000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450748

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721452

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.046

D;D

Polyphen

0.010

B;.

Vest4

0.68

MutPred

0.75

Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);

MVP

0.45

MPC

0.25

ClinPred

0.95

GERP RS

0.28

Varity_R

0.25

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.40

Position offset: -20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over