chr22-18910955-G-A

Variant names:

• chr22-18910955-G-A
• rs139729355
• NM_005675.6:c.440G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005675.6(DGCR6):​c.440G>A​(p.Arg147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.95
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010943532).
• BP6: Variant 22-18910955-G-A is Benign according to our data. Variant chr22-18910955-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2652850.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005675.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	NM_005675.6	MANE Select	c.440G>A	p.Arg147Gln	missense	Exon 4 of 5	NP_005666.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	ENST00000331444.12	TSL:1 MANE Select	c.440G>A	p.Arg147Gln	missense	Exon 4 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.440G>A	p.Arg147Gln	missense	Exon 4 of 6	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.32G>A	p.Arg11Gln	missense	Exon 4 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 1 AN: 11692 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00244 AC: 610 AN: 250050 AF XY: 0.00249

Gnomad AFR exome AF: 0.000867

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000510

Gnomad NFE exome AF: 0.00443

Gnomad OTH exome AF: 0.00345

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000137 AC: 1 AN: 73206 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38508

African (AFR) AF: 0.000119 AC: 1 AN: 8386

American (AMR) AF: 0.00 AC: 0 AN: 2686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1726

East Asian (EAS) AF: 0.00 AC: 0 AN: 4082

South Asian (SAS) AF: 0.00 AC: 0 AN: 9262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 526

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36852

Other (OTH) AF: 0.00 AC: 0 AN: 5102

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000855 AC: 1 AN: 11692 Hom.: 0 Cov.: 0 AF XY: 0.000190 AC XY: 1 AN XY: 5274

African (AFR) AF: 0.000136 AC: 1 AN: 7352

American (AMR) AF: 0.00 AC: 0 AN: 610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 154

East Asian (EAS) AF: 0.00 AC: 0 AN: 194

South Asian (SAS) AF: 0.00 AC: 0 AN: 216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 38

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2774

Other (OTH) AF: 0.00 AC: 0 AN: 138

Alfa AF: 0.00305 Hom.: 0

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00240 AC: 291

EpiCase AF: 0.00453

EpiControl AF: 0.00439

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.94	N
PhyloP100		3.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.10
Sift	Benign	0.89	T
Sift4G	Benign	1.0	T
Polyphen		0.030	B
Vest4		0.21
MVP		0.41
MPC		0.12
ClinPred		0.015	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.32
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs139729355; hg19: chr22-18898468; COSMIC: COSV99044995; COSMIC: COSV99044995;