chr1-15656623-A-G

Variant names:

• chr1-15656623-A-G
• NM_032341.5:c.1190A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032341.5(DDI2):​c.1190A>G​(p.Gln397Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DDI2 NM_032341.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09577775).

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.1190A>G	p.Gln397Arg	missense	Exon 9 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.1190A>G	p.Gln397Arg	missense	Exon 9 of 10	ENSP00000417748.1	Q5TDH0-1
	DDI2	ENST00000711099.1		c.1188A>G	p.Ser396Ser	synonymous	Exon 9 of 10	ENSP00000518577.1	A0AA34QVV2
	DDI2	ENST00000711098.1		c.1184-3214A>G		intron	N/A	ENSP00000518576.1	A0AA34QVL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461852 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

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	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.12
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.10		Gain of MoRF binding (P = 0.0229)
MVP		0.52
MPC		0.97
ClinPred		0.33	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.19
Mutation Taster		=71/29	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

hg19: chr1-15983118;