Variant 22-18910955-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005675.6(DGCR6):c.440G>A(p.Arg147Gln) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DGCR6
NM_005675.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.95

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]

DGCR6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010943532).

BP6

Variant 22-18910955-G-A is Benign according to our data. Variant chr22-18910955-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652850.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-18910955-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR6	NM_005675.6 linkuse as main transcript	c.440G>A	p.Arg147Gln	missense_variant	4/5	ENST00000331444.12
DGCR6	XM_047441510.1 linkuse as main transcript	c.233G>A	p.Arg78Gln	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR6	ENST00000331444.12 linkuse as main transcript	c.440G>A	p.Arg147Gln	missense_variant	4/5	1	NM_005675.6	P1	Q14129-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

11692

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00244

AC:

610

AN:

250050

Hom.:

AF XY:

0.00249

AC XY:

338

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.000867

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000137

AC:

AN:

73206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

38508

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN 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: AS_VQSR

AF:

0.0000855

AC:

AN:

11692

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

5274

show subpopulations

Gnomad4 AFR

AF:

0.000136

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:

0.00304

Hom.:

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00240

AC:

291

EpiCase

AF:

0.00453

EpiControl

AF:

0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DGCR6: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.0060

T;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.90

D;.;D

M_CAP

Benign

0.0025

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

1.5

N;N;.

Sift

Benign

0.89

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.030

.;B;.

Vest4

0.21

MVP

0.41

MPC

0.12

ClinPred

0.015

GERP RS

3.3

Varity_R

0.12

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over