20-62881627-G-A

Position:

• chr20-62881627-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001193369.2(DIDO1):​c.4329C>T​(p.Asp1443=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,612,542 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (154 hom.)
• Consequence: DIDO1 NM_001193369.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.82

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 20-62881627-G-A is Benign according to our data. Variant chr20-62881627-G-A is described in ClinVar as [Benign]. Clinvar id is 769108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIDO1	NM_001193369.2	c.4329C>T	p.Asp1443=	synonymous_variant	16/16	ENST00000395343.6	NP_001180298.1
DIDO1	NM_033081.3	c.4329C>T	p.Asp1443=	synonymous_variant	16/16		NP_149072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6	c.4329C>T	p.Asp1443=	synonymous_variant	16/16	1	NM_001193369.2	ENSP00000378752	P2
DIDO1	ENST00000266070.8	c.4329C>T	p.Asp1443=	synonymous_variant	16/16	5		ENSP00000266070	P2

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3745 AN: 152138 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00669 AC: 1676 AN: 250542 Hom.: 72 AF XY: 0.00485 AC XY: 658 AN XY: 135714

Gnomad AFR exome AF: 0.0924

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00258 AC: 3765 AN: 1460286 Hom.: 154 Cov.: 36 AF XY: 0.00221 AC XY: 1603 AN XY: 726470

Gnomad4 AFR exome AF: 0.0919

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.0247 AC: 3766 AN: 152256 Hom.: 146 Cov.: 32 AF XY: 0.0240 AC XY: 1790 AN XY: 74462

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0136 Hom.: 37

Bravo AF: 0.0275

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.9
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80326045; hg19: chr20-61512979;