chr22-18911670-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_005675.6(DGCR6):c.644G>C(p.Gly215Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Consequence
DGCR6
NM_005675.6 missense
NM_005675.6 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: -0.976
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 -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.050872058).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR6 | NM_005675.6 | c.644G>C | p.Gly215Ala | missense_variant | 5/5 | ENST00000331444.12 | |
DGCR6 | XM_047441510.1 | c.437G>C | p.Gly146Ala | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR6 | ENST00000331444.12 | c.644G>C | p.Gly215Ala | missense_variant | 5/5 | 1 | NM_005675.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD3 exomes AF: 0.0000258 AC: 6AN: 232244Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126352
GnomAD3 exomes
AF:
AC:
6
AN:
232244
Hom.:
AF XY:
AC XY:
2
AN XY:
126352
Gnomad AFR exome
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GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
ExAC
?
AF:
AC:
2
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 14, 2023 | The c.644G>C (p.G215A) alteration is located in exon 5 (coding exon 5) of the DGCR6 gene. This alteration results from a G to C substitution at nucleotide position 644, causing the glycine (G) at amino acid position 215 to be replaced by an alanine (A). 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
Benign
Dann
Benign
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
0.0010
.;B
Vest4
MutPred
0.13
.;Gain of loop (P = 0.1069);
MVP
MPC
0.11
ClinPred
T
GERP RS
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