rs374174945

Variant names:

• chr13-113458042-C-A
• NM_001014283.2:c.767G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-113458042-C-A
• chr13-113458042-C-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.767G>T​(p.Arg256Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R256H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCUN1D2 NM_001014283.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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]

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=0.09177706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCUN1D2	NM_001014283.2	c.767G>T	p.Arg256Leu	missense_variant	Exon 7 of 7	ENST00000478244.6	NP_001014305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCUN1D2	ENST00000478244.6	c.767G>T	p.Arg256Leu	missense_variant	Exon 7 of 7	1	NM_001014283.2	ENSP00000417706.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461728 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.037	.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.11
Sift	Benign	0.18	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.081	.;B
Vest4		0.27
MutPred		0.30		.;Gain of catalytic residue at L258 (P = 0);
MVP		0.17
MPC		0.23
ClinPred		0.24	T
GERP RS		0.56
Varity_R		0.17
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-114112357;