22-19041137-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005137.3(DGCR2):c.1317G>A(p.Pro439=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.42

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]

ACMG classification

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 GnomAd at 579 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR2	NM_005137.3	c.1317G>A	p.Pro439=	synonymous_variant	9/10	ENST00000263196.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR2	ENST00000263196.12	c.1317G>A	p.Pro439=	synonymous_variant	9/10	1	NM_005137.3	P1
DGCR2	ENST00000389262.8	c.*888G>A		3_prime_UTR_variant, NMD_transcript_variant	10/11	1
DGCR2	ENST00000537045.5	c.1194G>A	p.Pro398=	synonymous_variant	8/9	2
DGCR2	ENST00000467659.1	n.1095G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 579 AN: 152152 Hom.: 2 Cov.: 33

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.: 5 AF XY: 0.00427 AC XY: 579 AN XY: 135580

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.: 40 Cov.: 31 AF XY: 0.00596 AC XY: 4337 AN XY: 727156

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.: 2 Cov.: 33 AF XY: 0.00348 AC XY: 259 AN XY: 74452

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.: 3

Bravo AF: 0.00357

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00556

EpiControl AF: 0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	DGCR2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

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

Other links and lift over

dbSNP: rs146218436; hg19: chr22-19028650;