rs761557025

Variant names:

• chr22-18910241-T-G
• rs761557025
• NM_005675.6:c.341T>G

Variant summary

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

The NM_005675.6(DGCR6):​c.341T>G​(p.Val114Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• 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=0.39679113).

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.341T>G	p.Val114Gly	missense	Exon 3 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.341T>G	p.Val114Gly	missense	Exon 3 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.341T>G	p.Val114Gly	missense	Exon 3 of 6	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.-68T>G		5_prime_UTR	Exon 3 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 5498 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: 0.0000289 AC: 7 AN: 242028 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000390

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 1 AN: 48448 Hom.: 0 Cov.: 0 AF XY: 0.0000374 AC XY: 1 AN XY: 26768

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

African (AFR) AF: 0.00 AC: 0 AN: 3702

American (AMR) AF: 0.00 AC: 0 AN: 2278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1162

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4876

South Asian (SAS) AF: 0.00 AC: 0 AN: 10304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 22086

Other (OTH) AF: 0.00 AC: 0 AN: 2880

⚠️ 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: 5498 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2310

African (AFR) AF: 0.00 AC: 0 AN: 2702

American (AMR) AF: 0.00 AC: 0 AN: 426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 94

East Asian (EAS) AF: 0.00 AC: 0 AN: 276

South Asian (SAS) AF: 0.00 AC: 0 AN: 236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 66

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 44

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1566

Other (OTH) AF: 0.00 AC: 0 AN: 80

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000248 AC: 3

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	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.15	T
Polyphen		0.85	P
Vest4		0.38
MutPred		0.59		Loss of catalytic residue at V114 (P = 0.014)
MVP		0.71
MPC		0.27
ClinPred		0.27	T
GERP RS		3.6
Varity_R		0.34
gMVP		0.46
Mutation Taster		=64/36	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: rs761557025; hg19: chr22-18897754;