rs2238754

chr22-19070633-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.203-2408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,266 control chromosomes in the GnomAD database, including 565 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 0.068 (565 hom., cov: 33)
• Consequence: DGCR2 NM_005137.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR2	NM_005137.3	c.203-2408G>A		intron_variant		ENST00000263196.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR2	ENST00000263196.12	c.203-2408G>A		intron_variant		1	NM_005137.3	P1
DGCR2	ENST00000389262.8	c.203-2408G>A		intron_variant, NMD_transcript_variant		1
DGCR2	ENST00000537045.5	c.80-2408G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10307 AN: 152148 Hom.: 567 Cov.: 33

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0677 AC: 10303 AN: 152266 Hom.: 565 Cov.: 33 AF XY: 0.0681 AC XY: 5066 AN XY: 74434

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0541

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0764 Hom.: 352

Bravo AF: 0.0616

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.3
Dann	Benign	0.48

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: rs2238754; hg19: chr22-19058146;