NM_177438.3:c.4206+7_4206+8dupTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_177438.3(DICER1):c.4206+7_4206+8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 26,818 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.048 ( 29 hom., cov: 30)

Exomes 𝑓: 0.018 ( 101 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.425

Publications

0 publications found

Variant links:

Genes affected

DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

DICER1 Gene-Disease associations (from GenCC):

DICER1-related tumor predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
pleuropulmonary blastoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
DICER1 syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DICER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 14-95099771-C-CAA is Benign according to our data. Variant chr14-95099771-C-CAA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 221129.We mark this variant Benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3 link	c.4206+7_4206+8dupTT		splice_region_variant, intron_variant	Intron 22 of 26	ENST00000343455.8	NP_803187.1	Q9UPY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8 link	c.4206+8_4206+9insTT		splice_region_variant, intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

1289

AN:

26738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0410

Gnomad EAS

AF:

0.0155

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.00540

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0394

Gnomad OTH

AF:

0.0461

GnomAD2 exomes

AF:

0.00964

AC:

1645

AN:

170614

AF XY:

0.00887

show subpopulations

Gnomad AFR exome

AF:

0.0358

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00414

Gnomad NFE exome

AF:

0.00623

Gnomad OTH exome

AF:

0.0115

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0183

AC:

4990

AN:

272402

Hom.:

101

Cov.:

AF XY:

0.0185

AC XY:

2470

AN XY:

133590

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0546

AC:

693

AN:

12700

American (AMR)

AF:

0.0487

AC:

240

AN:

4924

Ashkenazi Jewish (ASJ)

AF:

0.0272

AC:

123

AN:

4516

East Asian (EAS)

AF:

0.0183

AC:

AN:

2402

South Asian (SAS)

AF:

0.0266

AC:

381

AN:

14336

European-Finnish (FIN)

AF:

0.00322

AC:

AN:

9006

Middle Eastern (MID)

AF:

0.0375

AC:

AN:

1574

European-Non Finnish (NFE)

AF:

0.0148

AC:

3128

AN:

211356

Other (OTH)

AF:

0.0253

AC:

293

AN:

11588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.353

Heterozygous variant carriers

241

482

722

963

1204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0484

AC:

1299

AN:

26818

Hom.:

Cov.:

AF XY:

0.0445

AC XY:

580

AN XY:

13022

show subpopulations

African (AFR)

AF:

0.0624

AC:

862

AN:

13822

American (AMR)

AF:

0.0344

AC:

AN:

2092

Ashkenazi Jewish (ASJ)

AF:

0.0410

AC:

AN:

536

East Asian (EAS)

AF:

0.0155

AC:

AN:

194

South Asian (SAS)

AF:

0.0367

AC:

AN:

682

European-Finnish (FIN)

AF:

0.00540

AC:

AN:

1852

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0394

AC:

279

AN:

7080

Other (OTH)

AF:

0.0452

AC:

AN:

420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00806

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:3

Jul 01, 2019

Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

ACMG criteria met: None -

Sep 06, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DICER1-related tumor predisposition

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 07, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pleuropulmonary blastoma

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_177438.3:c.4206+7_4206+8dupTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over