NM_177438.3:c.2660C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_177438.3(DICER1):c.2660C>A(p.Ser887Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S887F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DICER1
NM_177438.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 9.48

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33139914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DICER1	NM_177438.3	MANE Select	c.2660C>A	p.Ser887Tyr	missense	Exon 17 of 27	NP_803187.1	Q9UPY3-1
DICER1	NM_001271282.3		c.2660C>A	p.Ser887Tyr	missense	Exon 17 of 27	NP_001258211.1	Q9UPY3-1
DICER1	NM_001291628.2		c.2660C>A	p.Ser887Tyr	missense	Exon 17 of 27	NP_001278557.1	Q9UPY3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DICER1	ENST00000343455.8	TSL:1 MANE Select	c.2660C>A	p.Ser887Tyr	missense	Exon 17 of 27	ENSP00000343745.3	Q9UPY3-1
DICER1	ENST00000393063.6	TSL:1	c.2660C>A	p.Ser887Tyr	missense	Exon 19 of 29	ENSP00000376783.1	Q9UPY3-1
DICER1	ENST00000527414.5	TSL:1	c.2660C>A	p.Ser887Tyr	missense	Exon 17 of 27	ENSP00000435681.1	Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149070

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250936

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000155

AC:

AN:

1291528

Hom.:

Cov.:

AF XY:

0.0000186

AC XY:

AN XY:

644910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29160

American (AMR)

AF:

0.00

AC:

AN:

41752

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22202

East Asian (EAS)

AF:

0.00

AC:

AN:

33638

South Asian (SAS)

AF:

0.00

AC:

AN:

83322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5124

European-Non Finnish (NFE)

AF:

0.0000194

AC:

AN:

981432

Other (OTH)

AF:

0.0000193

AC:

AN:

51932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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: AC0

AF:

0.00

AC:

AN:

149220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72912

African (AFR)

AF:

0.00

AC:

AN:

40896

American (AMR)

AF:

0.00

AC:

AN:

14900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

4658

South Asian (SAS)

AF:

0.00

AC:

AN:

4282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67390

Other (OTH)

AF:

0.00

AC:

AN:

2106

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (2)

DICER1-related tumor predisposition (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

9.5

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.43

Sift

Uncertain

0.015

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.59

MVP

0.80

MPC

1.4

ClinPred

0.96

GERP RS

5.9

Varity_R

0.76

gMVP

0.65

Mutation Taster

=25/75

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over