rs9605062

Positions:

• chr22-20102357-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.1789-3820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,034 control chromosomes in the GnomAD database, including 5,677 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 0.27 (5677 hom., cov: 32)
• Consequence: DGCR8 NM_022720.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.1789-3820T>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.1789-3820T>C		intron_variant		1	NM_022720.7	ENSP00000263209	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41098 AN: 151916 Hom.: 5674 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41126 AN: 152034 Hom.: 5677 Cov.: 32 AF XY: 0.271 AC XY: 20161 AN XY: 74332

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.286

Alfa AF: 0.262 Hom.: 857

Bravo AF: 0.267

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.053
DANN	Benign	0.22
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: rs9605062; hg19: chr22-20089880; COSMIC: COSV61228878; COSMIC: COSV61228878;