chr22-20086301-A-G
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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):āc.338A>Gā(p.Lys113Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000060 ( 0 hom. )
Consequence
DGCR8
NM_022720.7 missense
NM_022720.7 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 6.88
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=0.17093444).
BS2
High AC in GnomAdExome4 at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR8 | NM_022720.7 | c.338A>G | p.Lys113Arg | missense_variant | 2/14 | ENST00000351989.8 | |
DGCR8 | NM_001190326.2 | c.338A>G | p.Lys113Arg | missense_variant | 2/13 | ||
DGCR8 | XM_047441418.1 | c.338A>G | p.Lys113Arg | missense_variant | 2/14 | ||
DGCR8 | XM_047441419.1 | c.338A>G | p.Lys113Arg | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR8 | ENST00000351989.8 | c.338A>G | p.Lys113Arg | missense_variant | 2/14 | 1 | NM_022720.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251274Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135860
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727238
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74284
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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 | Jun 06, 2023 | The c.338A>G (p.K113R) alteration is located in exon 2 (coding exon 1) of the DGCR8 gene. This alteration results from a A to G substitution at nucleotide position 338, causing the lysine (K) at amino acid position 113 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
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
Uncertain
T
PROVEAN
Benign
N;N;D;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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