rs745445238

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_177438.3(DICER1):c.4206+9_4206+13delGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 26 hom., cov: 0)

Exomes 𝑓: 0.12 ( 776 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.918

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 -8 ACMG points.

BP6

Variant 14-95099766-ACACAC-A is Benign according to our data. Variant chr14-95099766-ACACAC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 429146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3 link	c.4206+9_4206+13delGTGTG		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+9_4206+13delGTGTG		intron_variant	Intron 22 of 26	1	NM_177438.3	ENSP00000343745.3		Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

1876

AN:

130922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.0181

Gnomad AMR

AF:

0.00951

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0105

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.0132

GnomAD2 exomes

AF:

0.0351

AC:

7362

AN:

209476

AF XY:

0.0360

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0418

Gnomad EAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.123

AC:

147255

AN:

1194126

Hom.:

776

AF XY:

0.125

AC XY:

73949

AN XY:

593282

show subpopulations

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

African (AFR)

AF:

0.0773

AC:

2059

AN:

26638

American (AMR)

AF:

0.127

AC:

4345

AN:

34330

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

2928

AN:

21570

East Asian (EAS)

AF:

0.110

AC:

2701

AN:

24536

South Asian (SAS)

AF:

0.140

AC:

9438

AN:

67388

European-Finnish (FIN)

AF:

0.109

AC:

4405

AN:

40330

Middle Eastern (MID)

AF:

0.0880

AC:

409

AN:

4646

European-Non Finnish (NFE)

AF:

0.124

AC:

114978

AN:

925166

Other (OTH)

AF:

0.121

AC:

5992

AN:

49522

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

Heterozygous variant carriers

9877

19755

29632

39510

49387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4050

8100

12150

16200

20250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0143

AC:

1877

AN:

131010

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

943

AN XY:

63440

show subpopulations

African (AFR)

AF:

0.0330

AC:

1122

AN:

34030

American (AMR)

AF:

0.00949

AC:

122

AN:

12858

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

AN:

3098

East Asian (EAS)

AF:

0.0102

AC:

AN:

3538

South Asian (SAS)

AF:

0.0304

AC:

121

AN:

3984

European-Finnish (FIN)

AF:

0.0110

AC:

AN:

8794

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00492

AC:

304

AN:

61726

Other (OTH)

AF:

0.0131

AC:

AN:

1830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DICER1-related tumor predisposition

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 19, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Hereditary cancer-predisposing syndrome

Benign:1

Nov 02, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.92

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.

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