22-20090340-T-C

Variant names:

• chr22-20090340-T-C
• rs2073779
• NM_022720.7:c.1306+82T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022720.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR8	NM_022720.7	MANE Select	c.1306+82T>C		intron	N/A	NP_073557.3
	DGCR8	NM_001190326.2		c.1306+82T>C		intron	N/A	NP_001177255.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR8	ENST00000351989.8	TSL:1 MANE Select	c.1306+82T>C		intron	N/A	ENSP00000263209.3
	DGCR8	ENST00000407755.2	TSL:1	c.1306+82T>C		intron	N/A	ENSP00000384726.1
	DGCR8	ENST00000495826.5	TSL:1	n.1928+82T>C		intron	N/A

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

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: 67 AN: 3612

European-Non Finnish (NFE) AF: 0.0293 AC: 29811 AN: 1017630

Other (OTH) AF: 0.0371 AC: 2011 AN: 54216

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

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: 59 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: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0300 AC: 2039 AN: 68028

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0399 Hom.: 31

Bravo AF: 0.0451

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
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)

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: rs2073779; hg19: chr22-20077863;