Genetic Variant DGCR2:p.Arg543Leu (chr22-19038890-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005137.3(DGCR2):c.1628G>T(p.Arg543Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R543H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DGCR2
NM_005137.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05314228).

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.1628G>T	p.Arg543Leu	missense	Exon 10 of 10	NP_005128.1	P98153-1
DGCR2	NM_001184781.2		c.1619G>T	p.Arg540Leu	missense	Exon 10 of 10	NP_001171710.1
DGCR2	NM_001173533.2		c.1505G>T	p.Arg502Leu	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.1628G>T	p.Arg543Leu	missense	Exon 10 of 10	ENSP00000263196.7	P98153-1
DGCR2	ENST00000389262.8	TSL:1	n.*1199G>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000373914.5	Q5CZ70
DGCR2	ENST00000389262.8	TSL:1	n.*1199G>T		3_prime_UTR	Exon 11 of 11	ENSP00000373914.5	Q5CZ70

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248388

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000165

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460546

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52354

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111874

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000490

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.018

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

0.42

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.0

REVEL

Benign

0.050

Sift

Benign

0.26

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.11

MutPred

0.34

Loss of MoRF binding (P = 0.0053)

MVP

0.52

MPC

0.33

ClinPred

0.036

GERP RS

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.033

gMVP

0.17

Mutation Taster

=95/5

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