rs2023634

Variant names:

• chr22-18984937-A-G
• rs2023634
• ENST00000440005.6:n.135-2820A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000440005.6(DGCR5):​n.135-2820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,230 control chromosomes in the GnomAD database, including 472 homozygotes. 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 0.077 (472 hom., cov: 33)
• Consequence: DGCR5 ENST00000440005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 24 publications found

Genes affected

DGCR5 (HGNC:16757): (DiGeorge syndrome critical region gene 5) Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR5	NR_002733.3	n.192-2820A>G		intron_variant	Intron 1 of 3
DGCR5	NR_024159.2	n.192-5783A>G		intron_variant	Intron 1 of 4
DGCR5	NR_026651.2	n.192-5783A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR5	ENST00000440005.6	n.135-2820A>G		intron_variant	Intron 1 of 5	1
DGCR5	ENST00000421572.2	n.145-899A>G		intron_variant	Intron 1 of 5	2
DGCR5	ENST00000438934.5	n.146-2820A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11748 AN: 152112 Hom.: 470 Cov.: 33

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0772 AC: 11755 AN: 152230 Hom.: 472 Cov.: 33 AF XY: 0.0733 AC XY: 5456 AN XY: 74418

African (AFR) AF: 0.0867 AC: 3599 AN: 41532

American (AMR) AF: 0.0604 AC: 924 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4812

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6184 AN: 68008

Other (OTH) AF: 0.0782 AC: 165 AN: 2110

Alfa AF: 0.0849 Hom.: 1903

Bravo AF: 0.0791

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2023634; hg19: chr22-18972450;