rs192585552

Variant names:

• chr21-33583699-T-C
• rs192585552
• NM_017613.4:c.786-33A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_017613.4(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 NM_017613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 2 publications found

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]

DONSON Gene-Disease associations (from GenCC):

• microcephaly, short stature, and limb abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000617 (94/152290) while in subpopulation AMR AF = 0.0015 (23/15290). AF 95% confidence interval is 0.00103. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017613.4. 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
	DONSON	NM_017613.4	MANE Select	c.786-33A>G		intron	N/A	NP_060083.1	Q9NYP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DONSON	ENST00000303071.10	TSL:1 MANE Select	c.786-33A>G		intron	N/A	ENSP00000307143.4	Q9NYP3-1
	DONSON	ENST00000442660.5	TSL:1	n.464+891A>G		intron	N/A	ENSP00000408788.1	H7C304
	DONSON	ENST00000444517.5	TSL:1	n.464+891A>G		intron	N/A	ENSP00000392405.1	H7C006

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

GnomAD2 exomes AF: 0.000494 AC: 106 AN: 214458 AF XY: 0.000486

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 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

African (AFR) AF: 0.000303 AC: 9 AN: 29720

American (AMR) AF: 0.000987 AC: 35 AN: 35458

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 40 AN: 23136

East Asian (EAS) AF: 0.00 AC: 0 AN: 38690

South Asian (SAS) AF: 0.0000667 AC: 5 AN: 74910

European-Finnish (FIN) AF: 0.000196 AC: 10 AN: 50968

Middle Eastern (MID) AF: 0.00244 AC: 13 AN: 5330

European-Non Finnish (NFE) AF: 0.000669 AC: 683 AN: 1020392

Other (OTH) AF: 0.000978 AC: 54 AN: 55234

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

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.00150 AC: 23 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68018

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.75
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs192585552; hg19: chr21-34956005;