Genetic Variant DGCR2:p.Asp509Tyr (chr22-19038993-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005137.3(DGCR2):c.1525G>T(p.Asp509Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,611,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DGCR2
NM_005137.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Publications

3 publications found

Variant links:

Genes affected

DGCR2 (HGNC:2845): (DiGeorge syndrome critical region gene 2) Deletions of the 22q11.2 have been associated with a wide range of developmental defects (notably DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome and isolated conotruncal cardiac defects) classified under the acronym CATCH 22. The DGCR2 gene encodes a novel putative adhesion receptor protein, which could play a role in neural crest cells migration, a process which has been proposed to be altered in DiGeorge syndrome. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

DGCR2 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DGCR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15159062).

BS2

High AC in GnomAd4 at 34 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005137.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGCR2	NM_005137.3	MANE Select	c.1525G>T	p.Asp509Tyr	missense	Exon 10 of 10	NP_005128.1	P98153-1
DGCR2	NM_001184781.2		c.1516G>T	p.Asp506Tyr	missense	Exon 10 of 10	NP_001171710.1
DGCR2	NM_001173533.2		c.1402G>T	p.Asp468Tyr	missense	Exon 9 of 9	NP_001167004.1	P98153-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGCR2	ENST00000263196.12	TSL:1 MANE Select	c.1525G>T	p.Asp509Tyr	missense	Exon 10 of 10	ENSP00000263196.7	P98153-1
DGCR2	ENST00000389262.8	TSL:1	n.*1096G>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000373914.5	Q5CZ70
DGCR2	ENST00000389262.8	TSL:1	n.*1096G>T		3_prime_UTR	Exon 11 of 11	ENSP00000373914.5	Q5CZ70

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000326

AC:

AN:

245452

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1459694

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33472

American (AMR)

AF:

0.0000449

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111442

Other (OTH)

AF:

0.0000332

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000223

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.000796

AC:

AN:

41470

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.97

PhyloP100

5.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.012

Polyphen

0.98

Vest4

0.43

MVP

0.84

MPC

1.0

ClinPred

0.21

GERP RS

5.4

Varity_R

0.46

gMVP

0.55

Mutation Taster

=67/33

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over