chr22-20315469-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033257.4(DGCR6L):c.380A>G(p.Glu127Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000524 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00055 ( 0 hom. )
Consequence
DGCR6L
NM_033257.4 missense
NM_033257.4 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 4.11
Genes affected
DGCR6L (HGNC:18551): (DiGeorge syndrome critical region gene 6 like) This gene, the result of a duplication at this locus, is one of two functional genes encoding nearly identical proteins that have similar expression patterns. The product of this gene is a protein that shares homology with the Drosophila gonadal protein, expressed in gonadal tissues and germ cells, and with the human laminin gamma-1 chain that functions in cell attachment and migration. This gene is located in a region of chromosome 22 implicated in the DiGeorge syndrome, one facet of a broader collection of anomalies referred to as the CATCH 22 syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6L | NM_033257.4 | c.380A>G | p.Glu127Gly | missense_variant | 4/5 | ENST00000248879.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6L | ENST00000248879.8 | c.380A>G | p.Glu127Gly | missense_variant | 4/5 | 1 | NM_033257.4 | P1 | |
DGCR6L | ENST00000443409.1 | c.279A>G | p.Gly93= | synonymous_variant, NMD_transcript_variant | 3/4 | 1 | |||
DGCR6L | ENST00000405465.3 | c.266A>G | p.Glu89Gly | missense_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152196Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.000356 AC: 89AN: 250250Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135546
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GnomAD4 exome AF: 0.000545 AC: 797AN: 1461132Hom.: 0 Cov.: 31 AF XY: 0.000527 AC XY: 383AN XY: 726902
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GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27AN XY: 74350
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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 | Feb 28, 2024 | The c.380A>G (p.E127G) alteration is located in exon 4 (coding exon 4) of the DGCR6L gene. This alteration results from a A to G substitution at nucleotide position 380, causing the glutamic acid (E) at amino acid position 127 to be replaced by a glycine (G). 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
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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