22-18906398-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_005675.6(DGCR6):​c.24G>A​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.034 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

DGCR6
NM_005675.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.232
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 22-18906398-G-A is Benign according to our data. Variant chr22-18906398-G-A is described in ClinVar as [Benign]. Clinvar id is 779194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.232 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGCR6NM_005675.6 linkc.24G>A p.Leu8Leu synonymous_variant 1/5 ENST00000331444.12 NP_005666.2 Q14129-1X5D7D2
DGCR6XM_047441509.1 linkc.24G>A p.Leu8Leu synonymous_variant 1/4 XP_047297465.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGCR6ENST00000331444.12 linkc.24G>A p.Leu8Leu synonymous_variant 1/51 NM_005675.6 ENSP00000331681.6 Q14129-1
ENSG00000283809ENST00000638240.1 linkc.24G>A p.Leu8Leu synonymous_variant 1/65 ENSP00000492446.1 A0A1W2PRQ8

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
0
Hom.:
0
Cov.:
0
FAILED QC
GnomAD3 exomes
AF:
0.00639
AC:
1344
AN:
210330
Hom.:
43
AF XY:
0.00464
AC XY:
534
AN XY:
114994
show subpopulations
Gnomad AFR exome
AF:
0.000321
Gnomad AMR exome
AF:
0.0416
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00181
Gnomad SAS exome
AF:
0.0000724
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000552
Gnomad OTH exome
AF:
0.00411
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0339
AC:
4
AN:
118
Hom.:
1
Cov.:
0
AF XY:
0.0395
AC XY:
3
AN XY:
76
show subpopulations
Gnomad4 AMR exome
AF:
0.182
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
0
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000195
Hom.:
0
Asia WGS
AF:
0.00116
AC:
4
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 27, 2017- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
8.9
DANN
Benign
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs187183577; hg19: chr22-18893911; API