rs2073779

Positions:

• chr22-20090340-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.1306+82T>C		intron_variant		ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.1306+82T>C		intron_variant		1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7133 AN: 152210 Hom.: 237 Cov.: 33

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

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.0862

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.0972

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0371

GnomAD4 genome AF: 0.0469 AC: 7147 AN: 152328 Hom.: 239 Cov.: 33 AF XY: 0.0502 AC XY: 3742 AN XY: 74482

Gnomad4 AFR AF: 0.0577

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0300

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0397 Hom.: 30

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
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2073779; hg19: chr22-20077863;