Variant 20-62880806-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001193369.2(DIDO1):c.5150G>A(p.Gly1717Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000855 in 1,612,762 control chromosomes in the GnomAD database, including 5 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 0.0044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 5 hom. )

Consequence

DIDO1
NM_001193369.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.477

Variant links:

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]

DIDO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033049285).

BP6

Variant 20-62880806-C-T is Benign according to our data. Variant chr20-62880806-C-T is described in ClinVar as [Benign]. Clinvar id is 783872.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000484 (707/1460560) while in subpopulation AFR AF= 0.0171 (573/33480). AF 95% confidence interval is 0.016. There are 5 homozygotes in gnomad4_exome. There are 293 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 672 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIDO1	NM_001193369.2 linkuse as main transcript	c.5150G>A	p.Gly1717Asp	missense_variant	16/16	ENST00000395343.6	NP_001180298.1	Q9BTC0-4
DIDO1	NM_033081.3 linkuse as main transcript	c.5150G>A	p.Gly1717Asp	missense_variant	16/16		NP_149072.2	Q9BTC0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6 linkuse as main transcript	c.5150G>A	p.Gly1717Asp	missense_variant	16/16	1	NM_001193369.2	ENSP00000378752.1		Q9BTC0-4
DIDO1	ENST00000266070.8 linkuse as main transcript	c.5150G>A	p.Gly1717Asp	missense_variant	16/16	5		ENSP00000266070.4		Q9BTC0-4

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00125

AC:

313

AN:

250282

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000484

AC:

707

AN:

1460560

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

293

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.00442

AC:

672

AN:

152202

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00510

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00161

AC:

195

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.52

DANN

Benign

0.75

DEOGEN2

Benign

0.073

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.35

T;.

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.021

Sift

Benign

0.13

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.24

B;B

Vest4

0.083

MVP

0.23

MPC

0.56

ClinPred

0.0027

GERP RS

-5.9

Varity_R

0.030

gMVP

0.20

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over