rs2073778

Variant names:

• chr22-20087052-C-T
• rs2073778
• ENST00000495826.5:n.1233C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000495826.5(DGCR8):​n.1233C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,396,062 control chromosomes in the GnomAD database, including 20,149 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 0.13 (2225 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17924 hom.)
• Consequence: DGCR8 ENST00000495826.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 18 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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7	c.721-110C>T		intron_variant	Intron 2 of 13	ENST00000351989.8	NP_073557.3
DGCR8	NM_001190326.2	c.721-110C>T		intron_variant	Intron 2 of 12		NP_001177255.1
DGCR8	XM_047441418.1	c.721-110C>T		intron_variant	Intron 2 of 13		XP_047297374.1
DGCR8	XM_047441419.1	c.721-110C>T		intron_variant	Intron 2 of 13		XP_047297375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8	c.721-110C>T		intron_variant	Intron 2 of 13	1	NM_022720.7	ENSP00000263209.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19806 AN: 152110 Hom.: 2219 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.147 AC: 182789 AN: 1243834 Hom.: 17924 Cov.: 18 AF XY: 0.149 AC XY: 91702 AN XY: 614734

African (AFR) AF: 0.0213 AC: 593 AN: 27802

American (AMR) AF: 0.356 AC: 10460 AN: 29400

Ashkenazi Jewish (ASJ) AF: 0.0871 AC: 1688 AN: 19382

East Asian (EAS) AF: 0.482 AC: 18315 AN: 37994

South Asian (SAS) AF: 0.248 AC: 16774 AN: 67576

European-Finnish (FIN) AF: 0.149 AC: 6799 AN: 45694

Middle Eastern (MID) AF: 0.0780 AC: 324 AN: 4156

European-Non Finnish (NFE) AF: 0.125 AC: 119705 AN: 959618

Other (OTH) AF: 0.156 AC: 8131 AN: 52212

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152228 Hom.: 2225 Cov.: 32 AF XY: 0.139 AC XY: 10352 AN XY: 74424

African (AFR) AF: 0.0275 AC: 1145 AN: 41572

American (AMR) AF: 0.256 AC: 3922 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2663 AN: 5142

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1602 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8582 AN: 68020

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.127 Hom.: 5111

Bravo AF: 0.134

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		-0.36
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: rs2073778; hg19: chr22-20074575;