Variant chr22-19041137-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005137.3(DGCR2):c.1317G>A(p.Pro439Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,976 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 40 hom. )

Consequence

DGCR2
NM_005137.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.42

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 links:

DGCR2 (HGNC:):

DGCR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 22-19041137-C-T is Benign according to our data. Variant chr22-19041137-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19041137-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.42 with no splicing effect.

BS2

High AC in GnomAd4 at 580 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR2	NM_005137.3 linkuse as main transcript	c.1317G>A	p.Pro439Pro	synonymous_variant	9/10	ENST00000263196.12	NP_005128.1	P98153-1Q8IWC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR2	ENST00000263196.12 linkuse as main transcript	c.1317G>A	p.Pro439Pro	synonymous_variant	9/10	1	NM_005137.3	ENSP00000263196.7		P98153-1

Frequencies

GnomAD3 genomes

AF:

0.00381

AC:

579

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00423

AC:

1061

AN:

250746

Hom.:

AF XY:

0.00427

AC XY:

579

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00528

Gnomad NFE exome

AF:

0.00683

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00614

AC:

8968

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00596

AC XY:

4337

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00275

Gnomad4 FIN exome

AF:

0.00450

Gnomad4 NFE exome

AF:

0.00730

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.00381

AC:

580

AN:

152270

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

259

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00669

Gnomad4 NFE

AF:

0.00656

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00495

Hom.:

Bravo

AF:

0.00357

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00556

EpiControl

AF:

0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	DGCR2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.6

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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