dbSNP rs148798642: DGCR6:p.Arg129Gln (chr22-18910901-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005675.6(DGCR6):c.386G>A(p.Arg129Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

DGCR6
NM_005675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

Publications

0 publications found

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:

ENSG00000283809 (HGNC:):

ENSG00000283809 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16747391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005675.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	NM_005675.6	MANE Select	c.386G>A	p.Arg129Gln	missense	Exon 4 of 5	NP_005666.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGCR6	ENST00000331444.12	TSL:1 MANE Select	c.386G>A	p.Arg129Gln	missense	Exon 4 of 5	ENSP00000331681.6	Q14129-1
ENSG00000283809	ENST00000638240.1	TSL:5	c.386G>A	p.Arg129Gln	missense	Exon 4 of 6	ENSP00000492446.1	A0A1W2PRQ8
DGCR6	ENST00000413981.5	TSL:1	c.-23G>A		5_prime_UTR	Exon 4 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

17718

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000402

AC:

AN:

248832

AF XY:

0.0000518

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

17718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8148

African (AFR)

AF:

0.00

AC:

AN:

11410

American (AMR)

AF:

0.00

AC:

AN:

934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

234

East Asian (EAS)

AF:

0.00

AC:

AN:

286

South Asian (SAS)

AF:

0.00

AC:

AN:

280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

4074

Other (OTH)

AF:

0.00

AC:

AN:

200

Alfa

AF:

0.0000990

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.015

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

4.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

REVEL

Benign

0.096

Sift

Benign

0.072

Sift4G

Benign

0.18

Polyphen

0.10

Vest4

0.41

MVP

0.58

MPC

0.12

ClinPred

0.068

GERP RS

3.7

Varity_R

0.20

gMVP

0.42

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over