dbSNP rs2073779: DGCR8:c.1306+82T>C (chr22-20090340-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022720.7(DGCR8):c.1306+82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,457,378 control chromosomes in the GnomAD database, including 1,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 239 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1102 hom. )

Consequence

DGCR8
NM_022720.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.247

Publications

2 publications found

Variant links:

Genes affected

DGCR8 (HGNC:2847): (DGCR8 microprocessor complex subunit) This gene encodes a subunit of the microprocessor complex which mediates the biogenesis of microRNAs from the primary microRNA transcript. The encoded protein is a double-stranded RNA binding protein that functions as the non-catalytic subunit of the microprocessor complex. This protein is required for binding the double-stranded RNA substrate and facilitates cleavage of the RNA by the ribonuclease III protein, Drosha. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

DGCR8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7 link	c.1306+82T>C		intron_variant	Intron 5 of 13	ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8 link	c.1306+82T>C		intron_variant	Intron 5 of 13	1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes

AF:

0.0469

AC:

7133

AN:

152210

Hom.:

237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0526

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.0903

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0300

Gnomad OTH

AF:

0.0372

GnomAD4 exome

AF:

0.0351

AC:

45822

AN:

1305050

Hom.:

1102

AF XY:

0.0343

AC XY:

22046

AN XY:

642944

show subpopulations

African (AFR)

AF:

0.0571

AC:

1659

AN:

29064

American (AMR)

AF:

0.0862

AC:

2415

AN:

28008

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

316

AN:

19526

East Asian (EAS)

AF:

0.0972

AC:

3758

AN:

38648

South Asian (SAS)

AF:

0.0202

AC:

1377

AN:

68182

European-Finnish (FIN)

AF:

0.0955

AC:

4408

AN:

46164

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

3612

European-Non Finnish (NFE)

AF:

0.0293

AC:

29811

AN:

1017630

Other (OTH)

AF:

0.0371

AC:

2011

AN:

54216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2233

4467

6700

8934

11167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1206

2412

3618

4824

6030

<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

AF:

0.0469

AC:

7147

AN:

152328

Hom.:

239

Cov.:

AF XY:

0.0502

AC XY:

3742

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0577

AC:

2398

AN:

41584

American (AMR)

AF:

0.0529

AC:

810

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3470

East Asian (EAS)

AF:

0.0907

AC:

470

AN:

5180

South Asian (SAS)

AF:

0.0211

AC:

102

AN:

4830

European-Finnish (FIN)

AF:

0.105

AC:

1110

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0300

AC:

2039

AN:

68028

Other (OTH)

AF:

0.0364

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

337

674

1012

1349

1686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0399

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.59

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over