chr22-18911685-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_005675.6(DGCR6):c.659C>T(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00072 ( 1 hom., cov: 0)
Exomes 𝑓: 0.00018 ( 4 hom. )
Failed GnomAD Quality Control
Consequence
DGCR6
NM_005675.6 missense
NM_005675.6 missense
Scores
2
1
14
Clinical Significance
Conservation
PhyloP100: -1.93
Genes affected
DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.017767638).
BP6
Variant 22-18911685-C-T is Benign according to our data. Variant chr22-18911685-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2349847.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6 | NM_005675.6 | c.659C>T | p.Pro220Leu | missense_variant | 5/5 | ENST00000331444.12 | |
DGCR6 | XM_047441510.1 | c.452C>T | p.Pro151Leu | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6 | ENST00000331444.12 | c.659C>T | p.Pro220Leu | missense_variant | 5/5 | 1 | NM_005675.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 8AN: 11102Hom.: 1 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0000742 AC: 16AN: 215728Hom.: 0 AF XY: 0.0000256 AC XY: 3AN XY: 117408
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000179 AC: 10AN: 55714Hom.: 4 Cov.: 0 AF XY: 0.000175 AC XY: 5AN XY: 28570
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000721 AC: 8AN: 11102Hom.: 1 Cov.: 0 AF XY: 0.000769 AC XY: 4AN XY: 5204
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
0.0
.;B
Vest4
MVP
MPC
0.46
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