chr13-113483914-T-A

Position:

• chr13-113483914-T-A

Variant summary

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

The NM_001014283.2(DCUN1D2):​c.146A>T​(p.Asp49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: DCUN1D2 NM_001014283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCUN1D2	NM_001014283.2	c.146A>T	p.Asp49Val	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.146A>T	p.Asp49Val	missense_variant	2/7	1	NM_001014283.2	ENSP00000417706.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

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

Jan 08, 2024

The c.146A>T (p.D49V) alteration is located in exon 2 (coding exon 2) of the DCUN1D2 gene. This alteration results from a A to T substitution at nucleotide position 146, causing the aspartic acid (D) at amino acid position 49 to be replaced by a valine (V). 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	-0.0083	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.86
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D;D;D
Sift4G	Benign	0.076	T;D;.
Polyphen		0.084	B;.;.
Vest4		0.60
MutPred		0.37		Gain of catalytic residue at F44 (P = 0.0042);.;.;
MVP		0.27
MPC		0.25
ClinPred		0.61	D
GERP RS		-0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1384682598; hg19: chr13-114138229;