chr21-33580277-G-C

Variant names:

• chr21-33580277-G-C
• rs7280365
• NM_017613.4:c.1351-715C>G

Variant summary

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

The NM_017613.4(DONSON):​c.1351-715C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 147,266 control chromosomes in the GnomAD database, including 11,073 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 0.38 (11073 hom., cov: 23)
• Consequence: DONSON NM_017613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DONSON	NM_017613.4	c.1351-715C>G		intron_variant	Intron 8 of 9	ENST00000303071.10	NP_060083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DONSON	ENST00000303071.10	c.1351-715C>G		intron_variant	Intron 8 of 9	1	NM_017613.4	ENSP00000307143.4

Frequencies

GnomAD3 genomes AF: 0.385 AC: 56650 AN: 147150 Hom.: 11086 Cov.: 23

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.385 AC: 56628 AN: 147266 Hom.: 11073 Cov.: 23 AF XY: 0.387 AC XY: 27724 AN XY: 71716

African (AFR) AF: 0.345 AC: 13695 AN: 39664

American (AMR) AF: 0.411 AC: 6080 AN: 14776

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1146 AN: 3414

East Asian (EAS) AF: 0.585 AC: 2874 AN: 4912

South Asian (SAS) AF: 0.436 AC: 2000 AN: 4584

European-Finnish (FIN) AF: 0.385 AC: 3796 AN: 9852

Middle Eastern (MID) AF: 0.325 AC: 87 AN: 268

European-Non Finnish (NFE) AF: 0.388 AC: 25948 AN: 66900

Other (OTH) AF: 0.354 AC: 710 AN: 2006

Alfa AF: 0.247 Hom.: 605

Bravo AF: 0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.66
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7280365; hg19: chr21-34952583;