chr22-18910223-G-A

Variant names:

• chr22-18910223-G-A
• rs759720916
• NM_005675.6:c.323G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005675.6(DGCR6):​c.323G>A​(p.Arg108Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.864

Genes affected

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

ENSG00000283809 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03906694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.323G>A	p.Arg108Gln	missense_variant	Exon 3 of 5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.442G>A	p.Gly148Ser	missense_variant	Exon 4 of 4		XP_047297465.1
DGCR6	XM_047441510.1	c.116G>A	p.Arg39Gln	missense_variant	Exon 3 of 5		XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.323G>A	p.Arg108Gln	missense_variant	Exon 3 of 5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.323G>A	p.Arg108Gln	missense_variant	Exon 3 of 6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000998 AC: 24 AN: 240592 Hom.: 0 AF XY: 0.0000687 AC XY: 9 AN XY: 131046

Gnomad AFR exome AF: 0.0000665

Gnomad AMR exome AF: 0.000503

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.000171

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 52326 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

Alfa AF: 0.0000356 Hom.: 0

ExAC AF: 0.0000910 AC: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.323G>A (p.R108Q) alteration is located in exon 3 (coding exon 3) of the DGCR6 gene. This alteration results from a G to A substitution at nucleotide position 323, causing the arginine (R) at amino acid position 108 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.26	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.079
Sift	Benign	0.13	T;.
Sift4G	Benign	0.39	T;.
Polyphen		0.10	B;.
Vest4		0.077
MVP		0.49
MPC		0.12
ClinPred		0.018	T
GERP RS		1.4
Varity_R		0.13
gMVP		0.28

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: rs759720916; hg19: chr22-18897736;