dbSNP rs3757: DGCR8:c.*1700G>A (chr22-20111808-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022720.7(DGCR8):c.*1700G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 204,996 control chromosomes in the GnomAD database, including 5,275 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 0.21 ( 3545 hom., cov: 31)

Exomes 𝑓: 0.22 ( 1730 hom. )

Consequence

DGCR8
NM_022720.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Variant links:

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 links:

ENSG00000243762 (HGNC:):

ENSG00000243762 links:

TRMT2A (HGNC:24974): (tRNA methyltransferase 2 homolog A) The protein encoded by this gene is of unknown function. However, it is orthologous to the mouse Trmt2a gene and contains an RNA methyltransferase domain. Expression of this gene varies during the cell cycle, with aberrant expression being a possible biomarker in certain breast cancers. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

TRMT2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR8	NM_022720.7 link	c.*1700G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000351989.8	NP_073557.3	Q8WYQ5-1
TRMT2A	NM_022727.6 link	c.*755C>T		downstream_gene_variant		ENST00000252136.12	NP_073564.3	Q8IZ69-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR8	ENST00000351989.8 link	c.*1700G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_022720.7	ENSP00000263209.3		Q8WYQ5-1
TRMT2A	ENST00000252136.12 link	c.*755C>T		downstream_gene_variant		1	NM_022727.6	ENSP00000252136.7		Q8IZ69-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31333

AN:

150656

Hom.:

3545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.223

AC:

12070

AN:

54224

Hom.:

1730

Cov.:

AF XY:

0.224

AC XY:

6070

AN XY:

27090

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.219

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.208

AC:

31341

AN:

150772

Hom.:

3545

Cov.:

AF XY:

0.209

AC XY:

15374

AN XY:

73606

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.234

Hom.:

3749

Bravo

AF:

0.208

Asia WGS

AF:

0.156

AC:

543

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over