chr13-113483876-T-C

Position:

• chr13-113483876-T-C

Variant summary

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

The NM_001014283.2(DCUN1D2):​c.184A>G​(p.Lys62Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCUN1D2 NM_001014283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

Genes affected

DCUN1D2 (HGNC:20328): (defective in cullin neddylation 1 domain containing 2) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DCUN1D2 (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=0.15759853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCUN1D2	NM_001014283.2	c.184A>G	p.Lys62Glu	missense_variant	2/7	ENST00000478244.6	NP_001014305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCUN1D2	ENST00000478244.6	c.184A>G	p.Lys62Glu	missense_variant	2/7	1	NM_001014283.2	ENSP00000417706.1

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

Feb 13, 2023

The c.184A>G (p.K62E) alteration is located in exon 2 (coding exon 2) of the DCUN1D2 gene. This alteration results from a A to G substitution at nucleotide position 184, causing the lysine (K) at amino acid position 62 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;.;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.065
Sift	Benign	0.25	T;T;D
Sift4G	Benign	0.64	T;D;.
Polyphen		0.0010	B;.;.
Vest4		0.36
MutPred		0.37		Loss of MoRF binding (P = 0.003);.;.;
MVP		0.50
MPC		0.24
ClinPred		0.33	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr13-114138191;