20-62909676-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193369.2. 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
	DIDO1	NM_001193369.2	MANE Select	c.1161+23G>C		intron	N/A	NP_001180298.1	Q9BTC0-4
	DIDO1	NM_033081.3		c.1161+23G>C		intron	N/A	NP_149072.2	Q9BTC0-4
	DIDO1	NM_001193370.2		c.1161+23G>C		intron	N/A	NP_001180299.1	Q9BTC0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIDO1	ENST00000395343.6	TSL:1 MANE Select	c.1161+23G>C		intron	N/A	ENSP00000378752.1	Q9BTC0-4
	DIDO1	ENST00000395340.5	TSL:1	c.1161+23G>C		intron	N/A	ENSP00000378749.1	Q9BTC0-1
	DIDO1	ENST00000354665.8	TSL:1	c.1161+23G>C		intron	N/A	ENSP00000346692.4	Q9BTC0-3

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

GnomAD2 exomes AF: 0.247 AC: 61745 AN: 249608 AF XY: 0.243

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 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

African (AFR) AF: 0.327 AC: 10885 AN: 33238

American (AMR) AF: 0.348 AC: 15473 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 10009 AN: 26004

East Asian (EAS) AF: 0.344 AC: 13622 AN: 39598

South Asian (SAS) AF: 0.257 AC: 22079 AN: 85858

European-Finnish (FIN) AF: 0.122 AC: 6490 AN: 53306

Middle Eastern (MID) AF: 0.411 AC: 2365 AN: 5748

European-Non Finnish (NFE) AF: 0.191 AC: 211432 AN: 1107684

Other (OTH) AF: 0.240 AC: 14448 AN: 60138

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

African (AFR) AF: 0.321 AC: 13327 AN: 41540

American (AMR) AF: 0.291 AC: 4444 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1742 AN: 5172

South Asian (SAS) AF: 0.252 AC: 1217 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10604

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13199 AN: 68012

Other (OTH) AF: 0.290 AC: 612 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.53
DANN	Benign	0.44
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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