rs1639585612

Variant names:

• chr1-15617675-T-A
• rs1639585612
• NM_032341.5:c.5T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032341.5(DDI2):​c.5T>A​(p.Leu2Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,186 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DDI2 NM_032341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• Publications: 0 publications found

Genes affected

DDI2 (HGNC:24578): (DNA damage inducible 1 homolog 2) Enables aspartic-type endopeptidase activity; identical protein binding activity; and ubiquitin binding activity. Involved in several processes, including cellular response to hydroxyurea; proteolysis; and regulation of DNA stability. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000294489 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3225511).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDI2	NM_032341.5	MANE Select	c.5T>A	p.Leu2Gln	missense	Exon 1 of 10	NP_115717.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDI2	ENST00000480945.6	TSL:2 MANE Select	c.5T>A	p.Leu2Gln	missense	Exon 1 of 10	ENSP00000417748.1	Q5TDH0-1
	DDI2	ENST00000486680.1	TSL:1	n.133T>A		non_coding_transcript_exon	Exon 1 of 4
	DDI2	ENST00000711098.1		c.5T>A	p.Leu2Gln	missense	Exon 1 of 9	ENSP00000518576.1	A0AA34QVL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383186 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686350

African (AFR) AF: 0.00 AC: 0 AN: 29376

American (AMR) AF: 0.00 AC: 0 AN: 37438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24102

East Asian (EAS) AF: 0.00 AC: 0 AN: 33390

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069436

Other (OTH) AF: 0.00 AC: 0 AN: 56428

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.24	N
REVEL	Benign	0.22
Sift	Uncertain	0.020	D
Sift4G	Benign	0.37	T
Polyphen		0.064	B
Vest4		0.51
MutPred		0.53		Gain of disorder (P = 0.0013)
MVP		0.95
MPC		1.5
ClinPred		0.93	D
GERP RS		4.4
PromoterAI		-0.091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.82
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs1639585612; hg19: chr1-15944170;