Genetic Variant NM_005675.6:c.362G>A (chr22-18910262-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.362G>A(p.Arg121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

DGCR6
NM_005675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.102

Publications

1 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=0.07161799).

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.362G>A	p.Arg121Gln	missense	Exon 3 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.362G>A	p.Arg121Gln	missense	Exon 3 of 5	ENSP00000331681.6	Q14129-1
ENSG00000283809	ENST00000638240.1	TSL:5	c.362G>A	p.Arg121Gln	missense	Exon 3 of 6	ENSP00000492446.1	A0A1W2PRQ8
DGCR6	ENST00000413981.5	TSL:1	c.-47G>A		5_prime_UTR	Exon 3 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

6350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

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:

0.0000714

AC:

AN:

237974

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000651

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000229

AC:

AN:

43588

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

24234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3088

American (AMR)

AF:

0.00239

AC:

AN:

2092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1064

East Asian (EAS)

AF:

0.00

AC:

AN:

4400

South Asian (SAS)

AF:

0.000313

AC:

AN:

9578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

19828

Other (OTH)

AF:

0.00

AC:

AN:

2530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.744

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000314

AC:

AN:

6376

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

AN XY:

2732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3702

American (AMR)

AF:

0.00452

AC:

AN:

442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

264

South Asian (SAS)

AF:

0.00

AC:

AN:

216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1474

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.0000711

Hom.:

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

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

0.067

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.028

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

M_CAP

Benign

0.0083

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.75

PhyloP100

-0.10

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.45

REVEL

Benign

0.041

Sift

Benign

0.36

Sift4G

Benign

0.59

Polyphen

0.062

Vest4

0.15

MutPred

0.51

Loss of MoRF binding (P = 0.181)

MVP

0.31

MPC

0.12

ClinPred

0.044

GERP RS

2.6

Varity_R

0.020

gMVP

0.23

Mutation Taster

=94/6

polymorphism

(source)

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

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