22-18910222-C-T

Variant names:

• chr22-18910222-C-T
• rs770971431
• ENST00000413981.5:c.-87C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000413981.5(DGCR6):​c.-87C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 ENST00000413981.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2621461).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000413981.5. 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.322C>T	p.Arg108Trp	missense	Exon 3 of 5	NP_005666.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	ENST00000413981.5	TSL:1	c.-87C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000402409.1	Q6FGH4
	DGCR6	ENST00000331444.12	TSL:1 MANE Select	c.322C>T	p.Arg108Trp	missense	Exon 3 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.322C>T	p.Arg108Trp	missense	Exon 3 of 6	ENSP00000492446.1	A0A1W2PRQ8

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 5252 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000125 AC: 3 AN: 240030 AF XY: 0.0000153

Gnomad AFR exome AF: 0.000134

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000195 AC: 1 AN: 51174 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28260

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000247 AC: 1 AN: 4050

American (AMR) AF: 0.00 AC: 0 AN: 2400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1204

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 10690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 23316

Other (OTH) AF: 0.00 AC: 0 AN: 3064

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 5252 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2186

African (AFR) AF: 0.00 AC: 0 AN: 2356

American (AMR) AF: 0.00 AC: 0 AN: 408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 96

East Asian (EAS) AF: 0.00 AC: 0 AN: 282

South Asian (SAS) AF: 0.00 AC: 0 AN: 252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 64

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 46

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1662

Other (OTH) AF: 0.00 AC: 0 AN: 78

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.1
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.055
Sift	Benign	0.050	D
Sift4G	Benign	0.10	T
Polyphen		0.13	B
Vest4		0.36
MutPred		0.68		Loss of MoRF binding (P = 0.0615)
MVP		0.48
MPC		0.10
ClinPred		0.93	D
GERP RS		2.6
Varity_R		0.19
gMVP		0.50
Mutation Taster		=51/49	polymorphism

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: rs770971431; hg19: chr22-18897735;