1-68477038-T-C

Position:

• chr1-68477038-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114120.3(DEPDC1):​c.2330A>G​(p.Lys777Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: DEPDC1 NM_001114120.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054799467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC1	NM_001114120.3	c.2330A>G	p.Lys777Arg	missense_variant	12/12	ENST00000456315.7	NP_001107592.1
DEPDC1	NM_017779.6	c.1478A>G	p.Lys493Arg	missense_variant	11/11		NP_060249.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC1	ENST00000456315.7	c.2330A>G	p.Lys777Arg	missense_variant	12/12	1	NM_001114120.3	ENSP00000412292.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.2330A>G (p.K777R) alteration is located in exon 12 (coding exon 12) of the DEPDC1 gene. This alteration results from a A to G substitution at nucleotide position 2330, causing the lysine (K) at amino acid position 777 to be replaced by an arginine (R). 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	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0059	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.55	N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.12
Sift	Benign	0.51	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0010	B;B
Vest4		0.063
MutPred		0.21		Loss of methylation at K777 (P = 0.0011);.;
MVP		0.79
MPC		0.10
ClinPred		0.070	T
GERP RS		1.5
Varity_R		0.030
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr1-68942721;