1-15666843-A-G

Position:

• chr1-15666843-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032341.5(DDI2):​c.*7053A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,096 control chromosomes in the GnomAD database, including 33,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33022 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: DDI2 NM_032341.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDI2	NM_032341.5	c.*7053A>G		3_prime_UTR_variant	10/10	ENST00000480945.6	NP_115717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDI2	ENST00000480945.6	c.*7053A>G		3_prime_UTR_variant	10/10	2	NM_032341.5	ENSP00000417748	P1
DDI2	ENST00000711098.1	c.*5121A>G		3_prime_UTR_variant	9/9			ENSP00000518576
DDI2	ENST00000711099.1	c.*6994A>G		3_prime_UTR_variant	10/10			ENSP00000518577

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99340 AN: 151978 Hom.: 32977 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.616

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.654 AC: 99439 AN: 152096 Hom.: 33022 Cov.: 33 AF XY: 0.655 AC XY: 48724 AN XY: 74362

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.619

Alfa AF: 0.620 Hom.: 50801

Bravo AF: 0.641

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs10492987; hg19: chr1-15993338;