20-62909676-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001193369.2(DIDO1):​c.1161+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DIDO1 NM_001193369.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>A		intron	N/A	NP_001180298.1	Q9BTC0-4
	DIDO1	NM_033081.3		c.1161+23G>A		intron	N/A	NP_149072.2	Q9BTC0-4
	DIDO1	NM_001193370.2		c.1161+23G>A		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>A		intron	N/A	ENSP00000378752.1	Q9BTC0-4
	DIDO1	ENST00000395340.5	TSL:1	c.1161+23G>A		intron	N/A	ENSP00000378749.1	Q9BTC0-1
	DIDO1	ENST00000354665.8	TSL:1	c.1161+23G>A		intron	N/A	ENSP00000346692.4	Q9BTC0-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456208 Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3 AN XY: 723494

African (AFR) AF: 0.0000301 AC: 1 AN: 33242

American (AMR) AF: 0.00 AC: 0 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107814

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;