22-18906397-T-G

Variant names:

• chr22-18906397-T-G
• NM_005675.6:c.23T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005675.6(DGCR6):​c.23T>G​(p.Leu8Trp) 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 (★). Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.886

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1648632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.23T>G	p.Leu8Trp	missense_variant	Exon 1 of 5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.23T>G	p.Leu8Trp	missense_variant	Exon 1 of 4		XP_047297465.1
DGCR6	XM_047441510.1	c.-384T>G		upstream_gene_variant			XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.23T>G	p.Leu8Trp	missense_variant	Exon 1 of 5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.23T>G	p.Leu8Trp	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

Dec 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23T>G (p.L8W) 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 23, causing the leucine (L) at amino acid position 8 to be replaced by a tryptophan (W). 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	0.079
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.033	T;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.81	.;.;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N;.;.
REVEL	Benign	0.042
Sift	Benign	0.14	T;.;.
Sift4G	Benign	0.13	T;T;.
Polyphen		0.60	P;.;.
Vest4		0.25
MutPred		0.34		Loss of disorder (P = 0.04);Loss of disorder (P = 0.04);Loss of disorder (P = 0.04);
MVP		0.35
MPC		0.38
ClinPred		0.34	T
GERP RS		1.5
Varity_R		0.052
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18893910;