rs372751234

Variant names:

• chr22-18910958-A-G
• rs372751234
• NM_005675.6:c.443A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005675.6(DGCR6):​c.443A>G​(p.Lys148Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000027 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4045658).

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.443A>G	p.Lys148Arg	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.443A>G	p.Lys148Arg	missense	Exon 4 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.443A>G	p.Lys148Arg	missense	Exon 4 of 6	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.35A>G	p.Lys12Arg	missense	Exon 4 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes AF: 0.0000864 AC: 1 AN: 11578 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000138

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000272 AC: 2 AN: 73490 Hom.: 1 Cov.: 0 AF XY: 0.0000516 AC XY: 2 AN XY: 38730

African (AFR) AF: 0.000238 AC: 2 AN: 8402

American (AMR) AF: 0.00 AC: 0 AN: 2688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1736

East Asian (EAS) AF: 0.00 AC: 0 AN: 4092

South Asian (SAS) AF: 0.00 AC: 0 AN: 9282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4596

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 37052

Other (OTH) AF: 0.00 AC: 0 AN: 5116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000864 AC: 1 AN: 11578 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 5234

African (AFR) AF: 0.000138 AC: 1 AN: 7252

American (AMR) AF: 0.00 AC: 0 AN: 606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 152

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 226

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2742

Other (OTH) AF: 0.00 AC: 0 AN: 140

Alfa AF: 0.0000843 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.029	D
Polyphen		0.70	P
Vest4		0.54
MVP		0.71
MPC		0.40
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.52
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs372751234; hg19: chr22-18898471; COSMIC: COSV58230033; COSMIC: COSV58230033;