22-20102669-A-T

Variant names:

• chr22-20102669-A-T
• rs9606250
• NM_022720.7:c.1789-3508A>T

Variant summary

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

The NM_022720.7(DGCR8):​c.1789-3508A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,104 control chromosomes in the GnomAD database, including 2,882 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 0.17 (2882 hom., cov: 32)
• Consequence: DGCR8 NM_022720.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.1789-3508A>T		intron_variant	Intron 9 of 13	ENST00000351989.8	NP_073557.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.1789-3508A>T		intron_variant	Intron 9 of 13	1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26296 AN: 151986 Hom.: 2883 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.173 AC: 26298 AN: 152104 Hom.: 2882 Cov.: 32 AF XY: 0.172 AC XY: 12770 AN XY: 74332

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.205

Alfa AF: 0.109 Hom.: 188

Bravo AF: 0.164

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.98
DANN	Benign	0.26

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: rs9606250; hg19: chr22-20090192;