1-68477965-T-G

Position:

• chr1-68477965-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114120.3(DEPDC1):​c.2120A>C​(p.Asn707Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DEPDC1 NM_001114120.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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 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=0.1242809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC1	NM_001114120.3	c.2120A>C	p.Asn707Thr	missense_variant	11/12	ENST00000456315.7	NP_001107592.1
DEPDC1	NM_017779.6	c.1268A>C	p.Asn423Thr	missense_variant	10/11		NP_060249.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC1	ENST00000456315.7	c.2120A>C	p.Asn707Thr	missense_variant	11/12	1	NM_001114120.3	ENSP00000412292.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 09, 2024

The c.2120A>C (p.N707T) alteration is located in exon 11 (coding exon 11) of the DEPDC1 gene. This alteration results from a A to C substitution at nucleotide position 2120, causing the asparagine (N) at amino acid position 707 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0098	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.064
Sift	Benign	0.37	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.046	B;B
Vest4		0.22
MutPred		0.37		Gain of phosphorylation at N707 (P = 0.032);.;
MVP		0.74
MPC		0.15
ClinPred		0.14	T
GERP RS		2.0
Varity_R		0.053
gMVP		0.16

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

Other links and lift over

dbSNP: rs772858841; hg19: chr1-68943648;