rs2238751

Positions:

• chr22-19070277-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR2	NM_005137.3	c.203-2052C>T		intron_variant		ENST00000263196.12	NP_005128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR2	ENST00000263196.12	c.203-2052C>T		intron_variant		1	NM_005137.3	ENSP00000263196.7
DGCR2	ENST00000389262.8	n.203-2052C>T		intron_variant		1		ENSP00000373914.5
DGCR2	ENST00000545799.5	c.203-2052C>T		intron_variant		5
DGCR2	ENST00000537045.5	c.80-2052C>T		intron_variant		2		ENSP00000440062.1

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

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.154

Alfa AF: 0.175 Hom.: 564

Bravo AF: 0.175

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.47

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: rs2238751; hg19: chr22-19057790;