Variant rs2287584 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001382508.1(DROSHA):c.3306A>G(p.Pro1102Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,610,786 control chromosomes in the GnomAD database, including 64,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 10126 hom., cov: 32)

Exomes 𝑓: 0.25 ( 54135 hom. )

Consequence

DROSHA
NM_001382508.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.487

Variant links:

Genes affected

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

DROSHA links:

DROSHA (HGNC:):

DROSHA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 5-31422900-T-C is Benign according to our data. Variant chr5-31422900-T-C is described in ClinVar as [Benign]. Clinvar id is 3060707.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.487 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1 linkuse as main transcript	c.3306A>G	p.Pro1102Pro	synonymous_variant	29/36	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5 linkuse as main transcript	c.3306A>G	p.Pro1102Pro	synonymous_variant	28/35		NP_037367.3	Q9NRR4-1
DROSHA	NM_001100412.2 linkuse as main transcript	c.3195A>G	p.Pro1065Pro	synonymous_variant	28/35		NP_001093882.1	Q9NRR4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8 linkuse as main transcript	c.3306A>G	p.Pro1102Pro	synonymous_variant	29/36	5	NM_001382508.1	ENSP00000339845.3		Q9NRR4-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50817

AN:

151982

Hom.:

10096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.310

AC:

75867

AN:

244744

Hom.:

13890

AF XY:

0.305

AC XY:

40517

AN XY:

132696

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.663

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.252

AC:

367262

AN:

1458686

Hom.:

54135

Cov.:

AF XY:

0.254

AC XY:

184062

AN XY:

725436

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.335

AC:

50894

AN:

152100

Hom.:

10126

Cov.:

AF XY:

0.340

AC XY:

25241

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.670

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.243

Hom.:

5727

Bravo

AF:

0.349

Asia WGS

AF:

0.534

AC:

1855

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DROSHA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.3

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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