20-62881068-C-T

Position:

• chr20-62881068-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001193369.2(DIDO1):​c.4888G>A​(p.Glu1630Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,608,416 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (32 hom.)
• Consequence: DIDO1 NM_001193369.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031928718).
• BP6: Variant 20-62881068-C-T is Benign according to our data. Variant chr20-62881068-C-T is described in ClinVar as [Benign]. Clinvar id is 733406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00138 (211/152350) while in subpopulation EAS AF= 0.0264 (137/5180). AF 95% confidence interval is 0.0228. There are 1 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIDO1	NM_001193369.2	c.4888G>A	p.Glu1630Lys	missense_variant	16/16	ENST00000395343.6	NP_001180298.1
DIDO1	NM_033081.3	c.4888G>A	p.Glu1630Lys	missense_variant	16/16		NP_149072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6	c.4888G>A	p.Glu1630Lys	missense_variant	16/16	1	NM_001193369.2	ENSP00000378752	P2
DIDO1	ENST00000266070.8	c.4888G>A	p.Glu1630Lys	missense_variant	16/16	5		ENSP00000266070	P2

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 152234 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00313 AC: 714 AN: 228466 Hom.: 12 AF XY: 0.00315 AC XY: 400 AN XY: 127026

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.000502

Gnomad ASJ exome AF: 0.00180

Gnomad EAS exome AF: 0.0274

Gnomad SAS exome AF: 0.00557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000189

Gnomad OTH exome AF: 0.00194

GnomAD4 exome AF: 0.00116 AC: 1691 AN: 1456066 Hom.: 32 Cov.: 32 AF XY: 0.00128 AC XY: 924 AN XY: 724446

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000516

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.00483

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.00138 AC: 211 AN: 152350 Hom.: 1 Cov.: 33 AF XY: 0.00146 AC XY: 109 AN XY: 74506

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000718 Hom.: 0

Bravo AF: 0.00161

ESP6500AA AF: 0.000262 AC: 1

ESP6500EA AF: 0.000129 AC: 1

ExAC AF: 0.00289 AC: 340

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.64
DEOGEN2	Benign	0.078	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T;.
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.033
Sift	Benign	0.34	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0060	B;B
Vest4		0.048
MVP		0.26
MPC		0.41
ClinPred		0.0030	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201746991; hg19: chr20-61512420;