22-18906398-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005675.6(DGCR6):c.24G>A(p.Leu8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.034 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.232

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 22-18906398-G-A is Benign according to our data. Variant chr22-18906398-G-A is described in ClinVar as [Benign]. Clinvar id is 779194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.232 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR6	NM_005675.6	c.24G>A	p.Leu8=	synonymous_variant	1/5	ENST00000331444.12
DGCR6	XM_047441509.1	c.24G>A	p.Leu8=	synonymous_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR6	ENST00000331444.12	c.24G>A	p.Leu8=	synonymous_variant	1/5	1	NM_005675.6	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 0 Hom.: 0 Cov.: 0 FAILED QC

GnomAD3 exomes AF: 0.00639 AC: 1344 AN: 210330 Hom.: 43 AF XY: 0.00464 AC XY: 534 AN XY: 114994

Gnomad AFR exome AF: 0.000321

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00181

Gnomad SAS exome AF: 0.0000724

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000552

Gnomad OTH exome AF: 0.00411

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0339 AC: 4 AN: 118 Hom.: 1 Cov.: 0 AF XY: 0.0395 AC XY: 3 AN XY: 76

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Alfa AF: 0.000195 Hom.: 0

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 27, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	8.9
Dann	Benign	0.96

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: rs187183577; hg19: chr22-18893911;