13-113483951-G-T

Position:

• chr13-113483951-G-T

Variant summary

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

The NM_001014283.2(DCUN1D2):​c.109C>A​(p.Leu37Ile) 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. 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: 3.62

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=0.20756307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCUN1D2	NM_001014283.2	c.109C>A	p.Leu37Ile	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.109C>A	p.Leu37Ile	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

Jan 30, 2024

The c.109C>A (p.L37I) alteration is located in exon 2 (coding exon 2) of the DCUN1D2 gene. This alteration results from a C to A substitution at nucleotide position 109, causing the leucine (L) at amino acid position 37 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.17	T;D;D
Sift4G	Benign	0.18	T;D;.
Polyphen		0.56	P;.;.
Vest4		0.50
MutPred		0.37		Gain of catalytic residue at R36 (P = 0.1058);.;.;
MVP		0.26
MPC		0.22
ClinPred		0.76	D
GERP RS		4.6
Varity_R		0.21
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr13-114138266;