NM_005137.3:c.203-2408G>A

Variant names:

• chr22-19070633-C-T
• rs2238754
• NM_005137.3:c.203-2408G>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.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
• Publications: 6 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=-0.89).
• 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 rank	MANE	Protein	UniProt
DGCR2	NM_005137.3	c.203-2408G>A		intron_variant	Intron 2 of 9	ENST00000263196.12	NP_005128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR2	ENST00000263196.12	c.203-2408G>A		intron_variant	Intron 2 of 9	1	NM_005137.3	ENSP00000263196.7
DGCR2	ENST00000389262.8	n.203-2408G>A		intron_variant	Intron 2 of 10	1		ENSP00000373914.5
DGCR2	ENST00000537045.5	c.80-2408G>A		intron_variant	Intron 1 of 8	2		ENSP00000440062.1

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

African (AFR) AF: 0.0158 AC: 655 AN: 41568

American (AMR) AF: 0.0541 AC: 827 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1295 AN: 5174

South Asian (SAS) AF: 0.0389 AC: 188 AN: 4832

European-Finnish (FIN) AF: 0.110 AC: 1170 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5650 AN: 68014

Other (OTH) AF: 0.0662 AC: 140 AN: 2116

Alfa AF: 0.0744 Hom.: 595

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
PhyloP100		-0.026
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: rs2238754; hg19: chr22-19058146;