NM_005137.3:c.1317G>A

Variant names:

• chr22-19041137-C-T
• rs146218436
• NM_005137.3:c.1317G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.42
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 773616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.42 with no splicing effect.
• BS2: High AC in GnomAd4 at 580 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR2	NM_005137.3	MANE Select	c.1317G>A	p.Pro439Pro	synonymous	Exon 9 of 10	NP_005128.1	P98153-1
	DGCR2	NM_001184781.2		c.1308G>A	p.Pro436Pro	synonymous	Exon 9 of 10	NP_001171710.1
	DGCR2	NM_001173533.2		c.1194G>A	p.Pro398Pro	synonymous	Exon 8 of 9	NP_001167004.1	P98153-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR2	ENST00000263196.12	TSL:1 MANE Select	c.1317G>A	p.Pro439Pro	synonymous	Exon 9 of 10	ENSP00000263196.7	P98153-1
	DGCR2	ENST00000389262.8	TSL:1	n.*888G>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000373914.5	Q5CZ70
	DGCR2	ENST00000389262.8	TSL:1	n.*888G>A		3_prime_UTR	Exon 10 of 11	ENSP00000373914.5	Q5CZ70

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

GnomAD2 exomes AF: 0.00423 AC: 1061 AN: 250746 AF XY: 0.00427

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 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

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.00197 AC: 88 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00275 AC: 237 AN: 86248

European-Finnish (FIN) AF: 0.00450 AC: 240 AN: 53374

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00730 AC: 8119 AN: 1111932

Other (OTH) AF: 0.00412 AC: 249 AN: 60388

GnomAD4 genome AF: 0.00381 AC: 580 AN: 152270 Hom.: 2 Cov.: 33 AF XY: 0.00348 AC XY: 259 AN XY: 74452

African (AFR) AF: 0.000794 AC: 33 AN: 41550

American (AMR) AF: 0.000914 AC: 14 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.00669 AC: 71 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.6
DANN	Benign	0.90
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs146218436; hg19: chr22-19028650; COSMIC: COSV107200929; COSMIC: COSV107200929;