rs417309

Positions:

• chr22-20111021-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_022720.7(DGCR8):​c.*913G>A variant causes a 3 prime UTR 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 NM_022720.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.08

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.*913G>A		3_prime_UTR_variant	14/14	ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.*913G>A		3_prime_UTR_variant	14/14	1	NM_022720.7	ENSP00000263209	P1
	ENST00000412713.1	n.326C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9180 AN: 152150 Hom.: 393 Cov.: 33

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.: 0 AF XY: 0.0736 AC XY: 9145 AN XY: 124244

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.0367

Gnomad4 SAS exome AF: 0.0393

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0823

Gnomad4 OTH exome AF: 0.0685

GnomAD4 genome AF: 0.0603 AC: 9185 AN: 152268 Hom.: 394 Cov.: 33 AF XY: 0.0602 AC XY: 4479 AN XY: 74454

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0863

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0734 Hom.: 649

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	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	18
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs417309; hg19: chr22-20098544;