chr22-20086214-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_022720.7(DGCR8):c.251G>A(p.Arg84His) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
DGCR8
NM_022720.7 missense
NM_022720.7 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.57
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, DGCR8
BP4
Computational evidence support a benign effect (MetaRNN=0.13270426).
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR8 | NM_022720.7 | c.251G>A | p.Arg84His | missense_variant | 2/14 | ENST00000351989.8 | |
DGCR8 | NM_001190326.2 | c.251G>A | p.Arg84His | missense_variant | 2/13 | ||
DGCR8 | XM_047441418.1 | c.251G>A | p.Arg84His | missense_variant | 2/14 | ||
DGCR8 | XM_047441419.1 | c.251G>A | p.Arg84His | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR8 | ENST00000351989.8 | c.251G>A | p.Arg84His | missense_variant | 2/14 | 1 | NM_022720.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152132Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727236
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.251G>A (p.R84H) alteration is located in exon 2 (coding exon 1) of the DGCR8 gene. This alteration results from a G to A substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;N
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;D;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;B
Vest4
MutPred
Gain of ubiquitination at K82 (P = 0.0645);Gain of ubiquitination at K82 (P = 0.0645);Gain of ubiquitination at K82 (P = 0.0645);Gain of ubiquitination at K82 (P = 0.0645);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at