rs2238751

Variant names:

• chr22-19070277-G-A
• rs2238751
• NM_005137.3:c.203-2052C>T

Variant summary

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

The NM_005137.3(DGCR2):​c.203-2052C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,200 control chromosomes in the GnomAD database, including 2,526 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 0.18 (2526 hom., cov: 33)
• Consequence: DGCR2 NM_005137.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 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.203-2052C>T		intron	N/A	NP_005128.1	P98153-1
	DGCR2	NM_001184781.2		c.203-2052C>T		intron	N/A	NP_001171710.1
	DGCR2	NM_001173533.2		c.80-2052C>T		intron	N/A	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.203-2052C>T		intron	N/A	ENSP00000263196.7	P98153-1
	DGCR2	ENST00000389262.8	TSL:1	n.203-2052C>T		intron	N/A	ENSP00000373914.5	Q5CZ70
	DGCR2	ENST00000935670.1		c.334+1223C>T		intron	N/A	ENSP00000605729.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26805 AN: 152082 Hom.: 2527 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.176 AC: 26807 AN: 152200 Hom.: 2526 Cov.: 33 AF XY: 0.175 AC XY: 13014 AN XY: 74390

African (AFR) AF: 0.163 AC: 6750 AN: 41534

American (AMR) AF: 0.156 AC: 2384 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.131 AC: 679 AN: 5182

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1563 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12897 AN: 67998

Other (OTH) AF: 0.154 AC: 325 AN: 2116

Alfa AF: 0.174 Hom.: 575

Bravo AF: 0.175

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.018
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: rs2238751; hg19: chr22-19057790;