22-18910922-C-T

Variant names:

• chr22-18910922-C-T
• rs763659279
• NM_005675.6:c.407C>T

Variant summary

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

The NM_005675.6(DGCR6):​c.407C>T​(p.Ala136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A136T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000030 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.980
• 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=0.16353843).

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.407C>T	p.Ala136Val	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.407C>T	p.Ala136Val	missense	Exon 4 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.407C>T	p.Ala136Val	missense	Exon 4 of 6	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.-2C>T		5_prime_UTR	Exon 4 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249964 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000300 AC: 2 AN: 66688 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 35276

African (AFR) AF: 0.00 AC: 0 AN: 7820

American (AMR) AF: 0.00 AC: 0 AN: 2324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1508

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.00 AC: 0 AN: 8986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 476

European-Non Finnish (NFE) AF: 0.0000600 AC: 2 AN: 33328

Other (OTH) AF: 0.00 AC: 0 AN: 4522

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

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	0.096
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.98
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.092
Sift	Benign	0.22	T
Sift4G	Benign	0.25	T
Polyphen		0.65	P
Vest4		0.18
MutPred		0.40		Loss of disorder (P = 0.09)
MVP		0.62
MPC		0.13
ClinPred		0.34	T
GERP RS		3.8
Varity_R		0.11
gMVP		0.24
Mutation Taster		=291/9	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: rs763659279; hg19: chr22-18898435;