20-62909676-C-G

Variant names:

• chr20-62909676-C-G
• rs2295001
• NM_001193369.2:c.1161+23G>C

Variant summary

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

The NM_001193369.2(DIDO1):​c.1161+23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,608,262 control chromosomes in the GnomAD database, including 40,196 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 0.25 (5120 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35076 hom.)
• Consequence: DIDO1 NM_001193369.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

Genes affected

DIDO1 (HGNC:2680): (death inducer-obliterator 1) Apoptosis, a major form of cell death, is an efficient mechanism for eliminating unwanted cells and is of central importance for development and homeostasis in metazoan animals. In mice, the death inducer-obliterator-1 gene is upregulated by apoptotic signals and encodes a cytoplasmic protein that translocates to the nucleus upon apoptotic signal activation. When overexpressed, the mouse protein induced apoptosis in cell lines growing in vitro. This gene is similar to the mouse gene and therefore is thought to be involved in apoptosis. Alternatively spliced transcripts have been found for this gene, encoding multiple isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIDO1	NM_001193369.2	c.1161+23G>C		intron_variant	Intron 4 of 15	ENST00000395343.6	NP_001180298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6	c.1161+23G>C		intron_variant	Intron 4 of 15	1	NM_001193369.2	ENSP00000378752.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37641 AN: 152112 Hom.: 5105 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.247 AC: 61745 AN: 249608 Hom.: 8526 AF XY: 0.243 AC XY: 32817 AN XY: 134968

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.211 AC: 306803 AN: 1456032 Hom.: 35076 Cov.: 32 AF XY: 0.213 AC XY: 153940 AN XY: 723390

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.248 AC: 37682 AN: 152230 Hom.: 5120 Cov.: 33 AF XY: 0.244 AC XY: 18189 AN XY: 74416

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.290

Alfa AF: 0.235 Hom.: 873

Bravo AF: 0.270

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.53
DANN	Benign	0.44

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: rs2295001; hg19: chr20-61541028; COSMIC: COSV56613374;