chr22-18906601-C-G

Position:

• chr22-18906601-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_005675.6(DGCR6):​c.147C>G​(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: -0.265

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.147C>G	p.Ser49Arg	missense_variant	2/5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.147C>G	p.Ser49Arg	missense_variant	2/4		XP_047297465.1
DGCR6	XM_047441510.1	c.-180C>G		upstream_gene_variant			XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.147C>G	p.Ser49Arg	missense_variant	2/5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.147C>G	p.Ser49Arg	missense_variant	2/6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10304 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6034

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.147C>G (p.S49R) alteration is located in exon 2 (coding exon 2) of the DGCR6 gene. This alteration results from a C to G substitution at nucleotide position 147, causing the serine (S) at amino acid position 49 to be replaced by an arginine (R). 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	Pathogenic	0.98
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.0080	D;.;.
Sift4G	Uncertain	0.021	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.68
MutPred		0.71		Gain of phosphorylation at T47 (P = 0.0922);Gain of phosphorylation at T47 (P = 0.0922);Gain of phosphorylation at T47 (P = 0.0922);
MVP		0.74
MPC		0.53
ClinPred		0.99	D
GERP RS		0.72
Varity_R		0.66
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18894114;