rs2287584

Variant names:

• chr5-31422900-T-C
• rs2287584
• NM_001382508.1:c.3306A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.487
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.3306A>G	p.Pro1102Pro	synonymous	Exon 29 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.3306A>G	p.Pro1102Pro	synonymous	Exon 28 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.3195A>G	p.Pro1065Pro	synonymous	Exon 28 of 35	NP_001093882.1	Q9NRR4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.3306A>G	p.Pro1102Pro	synonymous	Exon 29 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.3306A>G	p.Pro1102Pro	synonymous	Exon 28 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.3195A>G	p.Pro1065Pro	synonymous	Exon 28 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50817 AN: 151982 Hom.: 10096 Cov.: 32

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

GnomAD2 exomes AF: 0.310 AC: 75867 AN: 244744 AF XY: 0.305

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 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.: 32 AF XY: 0.254 AC XY: 184062 AN XY: 725436

African (AFR) AF: 0.535 AC: 17862 AN: 33396

American (AMR) AF: 0.341 AC: 15063 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7755 AN: 26016

East Asian (EAS) AF: 0.708 AC: 28040 AN: 39610

South Asian (SAS) AF: 0.368 AC: 31554 AN: 85770

European-Finnish (FIN) AF: 0.249 AC: 13271 AN: 53250

Middle Eastern (MID) AF: 0.332 AC: 1910 AN: 5752

European-Non Finnish (NFE) AF: 0.211 AC: 234457 AN: 1110468

Other (OTH) AF: 0.288 AC: 17350 AN: 60284

GnomAD4 genome AF: 0.335 AC: 50894 AN: 152100 Hom.: 10126 Cov.: 32 AF XY: 0.340 AC XY: 25241 AN XY: 74346

African (AFR) AF: 0.515 AC: 21372 AN: 41474

American (AMR) AF: 0.326 AC: 4985 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3466

East Asian (EAS) AF: 0.670 AC: 3468 AN: 5174

South Asian (SAS) AF: 0.376 AC: 1809 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2742 AN: 10568

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14396 AN: 68018

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.261 Hom.: 17012

Bravo AF: 0.349

Asia WGS AF: 0.534 AC: 1855 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DROSHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.49
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287584; hg19: chr5-31423007; COSMIC: COSV60772682;