rs2073776

chr22-19037138-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR2	NM_005137.3	c.*1727G>A		3_prime_UTR_variant	10/10	ENST00000263196.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR2	ENST00000263196.12	c.*1727G>A		3_prime_UTR_variant	10/10	1	NM_005137.3	P1
DGCR2	ENST00000389262.8	c.*2951G>A		3_prime_UTR_variant, NMD_transcript_variant	11/11	1
DGCR2	ENST00000537045.5	c.*1727G>A		3_prime_UTR_variant	9/9	2

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.381

Alfa AF: 0.343 Hom.: 9538

Bravo AF: 0.435

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.15
Dann	Benign	0.59

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: rs2073776; hg19: chr22-19024651;