dbSNP rs417309: DGCR8:n.3844G>A (chr22-20111021-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000495826.5(DGCR8):n.3844G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0687 in 397,406 control chromosomes in the GnomAD database, including 1,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 394 hom., cov: 33)

Exomes 𝑓: 0.074 ( 736 hom. )

Consequence

DGCR8
ENST00000495826.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.08

Publications

38 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:

ENSG00000243762 (HGNC:):

ENSG00000243762 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 22-20111021-G-A is Benign according to our data. Variant chr22-20111021-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7 link	c.*913G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000351989.8	NP_073557.3	Q8WYQ5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8 link	c.*913G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_022720.7	ENSP00000263209.3		Q8WYQ5-1

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

9180

AN:

152150

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0368

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.0400

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0863

Gnomad OTH

AF:

0.0469

GnomAD4 exome

AF:

0.0739

AC:

18127

AN:

245138

Hom.:

736

Cov.:

AF XY:

0.0736

AC XY:

9145

AN XY:

124244

show subpopulations

African (AFR)

AF:

0.0163

AC:

117

AN:

7180

American (AMR)

AF:

0.0310

AC:

230

AN:

7428

Ashkenazi Jewish (ASJ)

AF:

0.0376

AC:

347

AN:

9236

East Asian (EAS)

AF:

0.0367

AC:

839

AN:

22882

South Asian (SAS)

AF:

0.0393

AC:

AN:

2188

European-Finnish (FIN)

AF:

0.111

AC:

2298

AN:

20740

Middle Eastern (MID)

AF:

0.0743

AC:

AN:

1292

European-Non Finnish (NFE)

AF:

0.0823

AC:

12995

AN:

157846

Other (OTH)

AF:

0.0685

AC:

1119

AN:

16346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

892

1784

2675

3567

4459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0603

AC:

9185

AN:

152268

Hom.:

394

Cov.:

AF XY:

0.0602

AC XY:

4479

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0193

AC:

802

AN:

41538

American (AMR)

AF:

0.0368

AC:

563

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3470

East Asian (EAS)

AF:

0.0403

AC:

209

AN:

5186

South Asian (SAS)

AF:

0.0340

AC:

164

AN:

4830

European-Finnish (FIN)

AF:

0.123

AC:

1309

AN:

10612

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0863

AC:

5871

AN:

68016

Other (OTH)

AF:

0.0488

AC:

103

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

443

885

1328

1770

2213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0719

Hom.:

1498

Bravo

AF:

0.0523

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23629745) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

4.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over