rs192585552

Positions:

• chr21-33583699-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000303071.10(DONSON):​c.786-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000635 in 1,486,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: DONSON ENST00000303071.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

Genes affected

DONSON (HGNC:2993): (DNA replication fork stabilization factor DONSON) This gene lies downstream of the SON gene and spans 10 kb on chromosome 21. The function of this gene is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DONSON	NM_017613.4	c.786-33A>G		intron_variant		ENST00000303071.10	NP_060083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DONSON	ENST00000303071.10	c.786-33A>G		intron_variant		1	NM_017613.4	ENSP00000307143	P1

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152172 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000494 AC: 106 AN: 214458 Hom.: 0 AF XY: 0.000486 AC XY: 57 AN XY: 117334

Gnomad AFR exome AF: 0.000346

Gnomad AMR exome AF: 0.000898

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000815

Gnomad FIN exome AF: 0.0000992

Gnomad NFE exome AF: 0.000548

Gnomad OTH exome AF: 0.000590

GnomAD4 exome AF: 0.000637 AC: 849 AN: 1333838 Hom.: 1 Cov.: 20 AF XY: 0.000665 AC XY: 442 AN XY: 664198

Gnomad4 AFR exome AF: 0.000303

Gnomad4 AMR exome AF: 0.000987

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000667

Gnomad4 FIN exome AF: 0.000196

Gnomad4 NFE exome AF: 0.000669

Gnomad4 OTH exome AF: 0.000978

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152290 Hom.: 0 Cov.: 30 AF XY: 0.000618 AC XY: 46 AN XY: 74486

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000825 Hom.: 0

Bravo AF: 0.00111

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs192585552; hg19: chr21-34956005;