5-60597787-T-A

Variant names:

• chr5-60597787-T-A
• NM_018369.3:c.1556A>T

Variant summary

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

The NM_018369.3(DEPDC1B):​c.1556A>T​(p.Gln519Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC1B NM_018369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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]

ACMG classification

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	c.1556A>T	p.Gln519Leu	missense_variant	Exon 11 of 11	ENST00000265036.10	NP_060839.2
DEPDC1B	NM_001145208.2	c.1370A>T	p.Gln457Leu	missense_variant	Exon 10 of 10		NP_001138680.1
DEPDC1B	XM_011543509.3	c.1511A>T	p.Gln504Leu	missense_variant	Exon 11 of 11		XP_011541811.1
DEPDC1B	XM_047417369.1	c.1325A>T	p.Gln442Leu	missense_variant	Exon 10 of 10		XP_047273325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC1B	ENST00000265036.10	c.1556A>T	p.Gln519Leu	missense_variant	Exon 11 of 11	1	NM_018369.3	ENSP00000265036.5
DEPDC1B	ENST00000453022.6	c.1370A>T	p.Gln457Leu	missense_variant	Exon 10 of 10	2		ENSP00000389101.2
DEPDC1B	ENST00000512078.5	n.*1367A>T		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000427527.1
DEPDC1B	ENST00000512078.5	n.*1367A>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000427527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1556A>T (p.Q519L) alteration is located in exon 11 (coding exon 11) of the DEPDC1B gene. This alteration results from a A to T substitution at nucleotide position 1556, causing the glutamine (Q) at amino acid position 519 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.67
MutPred		0.15		Loss of MoRF binding (P = 0.1081);.;
MVP		0.44
MPC		0.66
ClinPred		0.95	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-59893614;