rs2540641

Variant names:

• chr22-18972171-C-A
• rs2540641
• ENST00000440005.6:n.134+1513C>A

Variant summary

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

The ENST00000783637.1(DGCR5):​n.157C>A variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 151,898 control chromosomes in the GnomAD database, including 385 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 0.070 (385 hom., cov: 33)
• Consequence: DGCR5 ENST00000783637.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000783637.1. 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
	DGCR5	NR_002733.3		n.191+1513C>A		intron	N/A
	DGCR5	NR_024159.2		n.191+1513C>A		intron	N/A
	DGCR5	NR_026651.2		n.191+1513C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR5	ENST00000440005.6	TSL:1	n.134+1513C>A		intron	N/A
	DGCR5	ENST00000783637.1		n.157C>A		splice_region non_coding_transcript_exon	Exon 3 of 9
	DGCR5	ENST00000421572.2	TSL:2	n.144+1513C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10613 AN: 151782 Hom.: 385 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0788

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.0790

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

GnomAD4 genome AF: 0.0699 AC: 10615 AN: 151898 Hom.: 385 Cov.: 33 AF XY: 0.0669 AC XY: 4965 AN XY: 74240

African (AFR) AF: 0.0558 AC: 2311 AN: 41418

American (AMR) AF: 0.0581 AC: 887 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 273 AN: 3466

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4814

European-Finnish (FIN) AF: 0.0456 AC: 483 AN: 10602

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0913 AC: 6192 AN: 67854

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

Alfa AF: 0.0821 Hom.: 753

Bravo AF: 0.0703

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.58
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism

Splicing

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: rs2540641;

hg19: chr22-18959684;