22-18906456-T-G

Variant names:

• chr22-18906456-T-G
• NM_005675.6:c.82T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005675.6(DGCR6):​c.82T>G​(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.522

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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.82T>G	p.Leu28Val	missense_variant	Exon 1 of 5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.82T>G	p.Leu28Val	missense_variant	Exon 1 of 4		XP_047297465.1
DGCR6	XM_047441510.1	c.-325T>G		upstream_gene_variant			XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.82T>G	p.Leu28Val	missense_variant	Exon 1 of 5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.82T>G	p.Leu28Val	missense_variant	Exon 1 of 6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82T>G (p.L28V) alteration is located in exon 1 (coding exon 1) of the DGCR6 gene. This alteration results from a T to G substitution at nucleotide position 82, causing the leucine (L) at amino acid position 28 to be replaced by a valine (V). 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	0.57
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	.;.;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.3	N;.;.
REVEL	Uncertain	0.41
Sift	Benign	0.036	D;.;.
Sift4G	Uncertain	0.057	T;T;.
Polyphen		1.0	D;.;.
Vest4		0.50
MutPred		0.85		Gain of methylation at K33 (P = 0.0623);Gain of methylation at K33 (P = 0.0623);Gain of methylation at K33 (P = 0.0623);
MVP		0.51
MPC		0.51
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.21
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: chr22-18893969;