chr22-20314794-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033257.4(DGCR6L):c.544C>T(p.Leu182Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,611,932 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 (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
DGCR6L
NM_033257.4 missense
NM_033257.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.02
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26305723).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6L | NM_033257.4 | c.544C>T | p.Leu182Phe | missense_variant | 5/5 | ENST00000248879.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6L | ENST00000248879.8 | c.544C>T | p.Leu182Phe | missense_variant | 5/5 | 1 | NM_033257.4 | P1 | |
DGCR6L | ENST00000443409.1 | c.*149C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 1 | ||||
DGCR6L | ENST00000405465.3 | c.430C>T | p.Leu144Phe | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
5
AN:
152230
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249402Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135092
GnomAD3 exomes
AF:
AC:
8
AN:
249402
Hom.:
AF XY:
AC XY:
3
AN XY:
135092
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000541 AC: 79AN: 1459702Hom.: 0 Cov.: 31 AF XY: 0.0000592 AC XY: 43AN XY: 726090
GnomAD4 exome
AF:
AC:
79
AN:
1459702
Hom.:
Cov.:
31
AF XY:
AC XY:
43
AN XY:
726090
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74360
GnomAD4 genome
?
AF:
AC:
5
AN:
152230
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
4
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 | Sep 16, 2021 | The c.544C>T (p.L182F) alteration is located in exon 5 (coding exon 5) of the DGCR6L gene. This alteration results from a C to T substitution at nucleotide position 544, causing the leucine (L) at amino acid position 182 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
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
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.1441);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at