1-15630337-T-C

Position:

• chr1-15630337-T-C

Variant summary

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

The NM_032341.5(DDI2):​c.281T>C​(p.Ile94Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDI2 NM_032341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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]

DDI2 (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
DDI2	NM_032341.5	c.281T>C	p.Ile94Thr	missense_variant	3/10	ENST00000480945.6	NP_115717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDI2	ENST00000480945.6	c.281T>C	p.Ile94Thr	missense_variant	3/10	2	NM_032341.5	ENSP00000417748.1
DDI2	ENST00000486680.1	n.409T>C		non_coding_transcript_exon_variant	3/4	1
DDI2	ENST00000711098.1	c.281T>C	p.Ile94Thr	missense_variant	3/9			ENSP00000518576.1
DDI2	ENST00000711099.1	c.281T>C	p.Ile94Thr	missense_variant	3/10			ENSP00000518577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 06, 2021

The c.281T>C (p.I94T) alteration is located in exon 3 (coding exon 3) of the DDI2 gene. This alteration results from a T to C substitution at nucleotide position 281, causing the isoleucine (I) at amino acid position 94 to be replaced by a threonine (T). 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.071
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.077	T
Sift4G	Benign	0.17	T
Polyphen		0.067	B
Vest4		0.90
MutPred		0.24		Loss of stability (P = 2e-04);
MVP		0.45
MPC		1.2
ClinPred		0.71	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.59

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: chr1-15956832;