22-18907714-C-T

Variant names:

• chr22-18907714-C-T
• rs418623
• NM_005675.6:c.271+989C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005675.6(DGCR6):​c.271+989C>T variant causes a intron 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: not found (cov: 7)
• Consequence: DGCR6 NM_005675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 20 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.271+989C>T		intron	N/A	NP_005666.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	ENST00000331444.12	TSL:1 MANE Select	c.271+989C>T		intron	N/A	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.271+989C>T		intron	N/A	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.-138+989C>T		intron	N/A	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 7

Alfa AF: 0.572 Hom.: 43109

Asia WGS AF: 0.224 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.62
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs418623;

hg19: chr22-18895227;