rs10483098

Positions:

• chr22-19014231-G-A
• chr22-19014231-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_110533.2(DGCR5):​n.742-122G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 699,296 control chromosomes in the GnomAD database, including 93 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 0.018 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (25 hom.)
• Consequence: DGCR5 NR_110533.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGCR5	NR_110533.2	n.742-122G>A		intron_variant, non_coding_transcript_variant
DGCR5	NR_024159.2	n.598-122G>A		intron_variant, non_coding_transcript_variant
DGCR5	NR_026651.2	n.598-122G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGCR5	ENST00000424407.1	n.426-122G>A		intron_variant, non_coding_transcript_variant		2
DGCR5	ENST00000675214.1	n.221-122G>A		intron_variant, non_coding_transcript_variant
DGCR5	ENST00000675671.1	n.910-122G>A		intron_variant, non_coding_transcript_variant
DGCR5	ENST00000675978.1	n.763-122G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2705 AN: 151788 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00735

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00261 AC: 1429 AN: 547414 Hom.: 25 AF XY: 0.00223 AC XY: 657 AN XY: 294160

Gnomad4 AFR exome AF: 0.0579

Gnomad4 AMR exome AF: 0.00355

Gnomad4 ASJ exome AF: 0.00896

Gnomad4 EAS exome AF: 0.0000668

Gnomad4 SAS exome AF: 0.000155

Gnomad4 FIN exome AF: 0.000333

Gnomad4 NFE exome AF: 0.000411

Gnomad4 OTH exome AF: 0.00457

GnomAD4 genome AF: 0.0179 AC: 2713 AN: 151882 Hom.: 68 Cov.: 32 AF XY: 0.0177 AC XY: 1315 AN XY: 74202

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.00735

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0162

Alfa AF: 0.00425 Hom.: 12

Bravo AF: 0.0205

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10483098; hg19: chr22-19001744;