chr22-19037138-C-T

Variant names:

• chr22-19037138-C-T
• rs2073776
• NM_005137.3:c.*1727G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005137.3(DGCR2):​c.*1727G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,162 control chromosomes in the GnomAD database, including 15,362 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (15360 hom., cov: 33)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: DGCR2 NM_005137.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

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.*1727G>A		3_prime_UTR	Exon 10 of 10	NP_005128.1
	DGCR2	NM_001184781.2		c.*1727G>A		3_prime_UTR	Exon 10 of 10	NP_001171710.1
	DGCR2	NM_001173533.2		c.*1727G>A		3_prime_UTR	Exon 9 of 9	NP_001167004.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR2	ENST00000263196.12	TSL:1 MANE Select	c.*1727G>A		3_prime_UTR	Exon 10 of 10	ENSP00000263196.7
	DGCR2	ENST00000389262.8	TSL:1	n.*2951G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000373914.5
	DGCR2	ENST00000389262.8	TSL:1	n.*2951G>A		3_prime_UTR	Exon 11 of 11	ENSP00000373914.5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64145 AN: 151932 Hom.: 15317 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.304 AC: 34 AN: 112 Hom.: 2 Cov.: 0 AF XY: 0.303 AC XY: 23 AN XY: 76

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.429 AC: 6 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.279 AC: 24 AN: 86

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.422 AC: 64238 AN: 152050 Hom.: 15360 Cov.: 33 AF XY: 0.422 AC XY: 31345 AN XY: 74312

African (AFR) AF: 0.656 AC: 27222 AN: 41496

American (AMR) AF: 0.364 AC: 5570 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1531 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1656 AN: 5152

South Asian (SAS) AF: 0.467 AC: 2251 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3130 AN: 10572

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21422 AN: 67944

Other (OTH) AF: 0.381 AC: 804 AN: 2108

Alfa AF: 0.357 Hom.: 15400

Bravo AF: 0.435

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.59
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs2073776; hg19: chr22-19024651;