Variant 20-62879717-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001193369.2(DIDO1):c.6239A>G(p.Asn2080Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,611,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

DIDO1
NM_001193369.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.235

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032087266).

BP6

Variant 20-62879717-T-C is Benign according to our data. Variant chr20-62879717-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 738874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 223 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIDO1	NM_001193369.2 linkuse as main transcript	c.6239A>G	p.Asn2080Ser	missense_variant	16/16	ENST00000395343.6	NP_001180298.1	Q9BTC0-4
DIDO1	NM_033081.3 linkuse as main transcript	c.6239A>G	p.Asn2080Ser	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.6239A>G	p.Asn2080Ser	missense_variant	16/16	1	NM_001193369.2	ENSP00000378752.1		Q9BTC0-4
DIDO1	ENST00000266070.8 linkuse as main transcript	c.6239A>G	p.Asn2080Ser	missense_variant	16/16	5		ENSP00000266070.4		Q9BTC0-4

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000387

AC:

AN:

245536

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

134020

show subpopulations

Gnomad AFR exome

AF:

0.00540

Gnomad AMR exome

AF:

0.000318

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1459376

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

726062

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.000447

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:

0.00000809

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152222

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00484

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000867

Hom.:

Bravo

AF:

0.00179

ESP6500AA

AF:

0.00579

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000489

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.42

DANN

Benign

0.33

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.71

T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.54

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.064

Sift

Benign

0.38

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0050

B;B

Vest4

0.018

MVP

0.29

MPC

0.29

ClinPred

0.0064

GERP RS

-11

Varity_R

0.012

gMVP

0.10

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