22-19089536-C-T

Variant names:

• chr22-19089536-C-T
• rs2800960
• NM_005137.3:c.80-46G>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.80-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,470,086 control chromosomes in the GnomAD database, including 619,209 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 0.93 (65954 hom., cov: 34)
  • Exomes 𝑓: 0.92 (553255 hom.)
• Consequence: DGCR2 NM_005137.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR2	NM_005137.3	c.80-46G>A		intron_variant	Intron 1 of 9	ENST00000263196.12	NP_005128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR2	ENST00000263196.12	c.80-46G>A		intron_variant	Intron 1 of 9	1	NM_005137.3	ENSP00000263196.7
DGCR2	ENST00000389262.8	n.80-46G>A		intron_variant	Intron 1 of 10	1		ENSP00000373914.5
DGCR2	ENST00000537045.5	c.80-21311G>A		intron_variant	Intron 1 of 8	2		ENSP00000440062.1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141505 AN: 152202 Hom.: 65903 Cov.: 34

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.926

GnomAD2 exomes AF: 0.914 AC: 153855 AN: 168254 AF XY: 0.915

Gnomad AFR exome AF: 0.982

Gnomad AMR exome AF: 0.901

Gnomad ASJ exome AF: 0.945

Gnomad EAS exome AF: 0.805

Gnomad FIN exome AF: 0.913

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.914

GnomAD4 exome AF: 0.916 AC: 1207009 AN: 1317766 Hom.: 553255 Cov.: 32 AF XY: 0.917 AC XY: 592819 AN XY: 646302

African (AFR) AF: 0.985 AC: 28275 AN: 28700

American (AMR) AF: 0.903 AC: 26461 AN: 29302

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 18762 AN: 19934

East Asian (EAS) AF: 0.820 AC: 27440 AN: 33482

South Asian (SAS) AF: 0.968 AC: 65414 AN: 67586

European-Finnish (FIN) AF: 0.913 AC: 44223 AN: 48452

Middle Eastern (MID) AF: 0.927 AC: 4681 AN: 5048

European-Non Finnish (NFE) AF: 0.913 AC: 942227 AN: 1031662

Other (OTH) AF: 0.924 AC: 49526 AN: 53600

GnomAD4 genome AF: 0.930 AC: 141613 AN: 152320 Hom.: 65954 Cov.: 34 AF XY: 0.928 AC XY: 69131 AN XY: 74470

African (AFR) AF: 0.982 AC: 40827 AN: 41578

American (AMR) AF: 0.902 AC: 13799 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3258 AN: 3472

East Asian (EAS) AF: 0.819 AC: 4237 AN: 5174

South Asian (SAS) AF: 0.965 AC: 4659 AN: 4826

European-Finnish (FIN) AF: 0.913 AC: 9689 AN: 10612

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 62075 AN: 68032

Other (OTH) AF: 0.927 AC: 1961 AN: 2116

Alfa AF: 0.919 Hom.: 43745

Bravo AF: 0.929

Asia WGS AF: 0.920 AC: 3201 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	1.0
DANN	Benign	0.58
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2800960; hg19: chr22-19077049;