22-18906708-T-A

Position:

• chr22-18906708-T-A

Variant summary

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

The NM_005675.6(DGCR6):​c.254T>A​(p.Leu85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 3.08

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.254T>A	p.Leu85Gln	missense_variant	2/5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.254T>A	p.Leu85Gln	missense_variant	2/4		XP_047297465.1
DGCR6	XM_047441510.1	c.-73T>A		5_prime_UTR_variant	1/5		XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.254T>A	p.Leu85Gln	missense_variant	2/5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.254T>A	p.Leu85Gln	missense_variant	2/6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000364 AC: 9 AN: 247504 Hom.: 0 AF XY: 0.0000372 AC XY: 5 AN XY: 134374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000165 AC: 2

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

Jan 26, 2023

The c.254T>A (p.L85Q) alteration is located in exon 2 (coding exon 2) of the DGCR6 gene. This alteration results from a T to A substitution at nucleotide position 254, causing the leucine (L) at amino acid position 85 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	.;.;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.3	D;.;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	D;.;.
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		1.0	D;.;.
Vest4		0.82
MutPred		0.67		Gain of disorder (P = 0.0212);Gain of disorder (P = 0.0212);Gain of disorder (P = 0.0212);
MVP		0.64
MPC		0.51
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.77
gMVP		0.68

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: rs367623093; hg19: chr22-18894221;