NM_005137.3:c.1579G>T

Variant names:

• chr22-19038939-C-A
• rs1360403860
• NM_005137.3:c.1579G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005137.3(DGCR2):​c.1579G>T​(p.Gly527Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G527R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DGCR2 NM_005137.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21742189).

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.1579G>T	p.Gly527Trp	missense	Exon 10 of 10	NP_005128.1	P98153-1
	DGCR2	NM_001184781.2		c.1570G>T	p.Gly524Trp	missense	Exon 10 of 10	NP_001171710.1
	DGCR2	NM_001173533.2		c.1456G>T	p.Gly486Trp	missense	Exon 9 of 9	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.1579G>T	p.Gly527Trp	missense	Exon 10 of 10	ENSP00000263196.7	P98153-1
	DGCR2	ENST00000389262.8	TSL:1	n.*1150G>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000373914.5	Q5CZ70
	DGCR2	ENST00000389262.8	TSL:1	n.*1150G>T		3_prime_UTR	Exon 11 of 11	ENSP00000373914.5	Q5CZ70

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460182 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726390

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111768

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.12
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.020	D
Polyphen		0.98	D
Vest4		0.28
MutPred		0.18		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.69
MPC		0.87
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.25
Mutation Taster		=86/14	polymorphism

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: rs1360403860; hg19: chr22-19026452;