rs779803447

Variant names:

• chr21-33583576-G-A
• rs779803447
• NM_017613.4:c.876C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-33583576-G-A
• chr21-33583576-G-C
• chr21-33583576-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017613.4(DONSON):​c.876C>T​(p.Phe292Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DONSON NM_017613.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.11).
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DONSON	NM_017613.4	MANE Select	c.876C>T	p.Phe292Phe	synonymous	Exon 5 of 10	NP_060083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DONSON	ENST00000303071.10	TSL:1 MANE Select	c.876C>T	p.Phe292Phe	synonymous	Exon 5 of 10	ENSP00000307143.4
	DONSON	ENST00000442660.5	TSL:1	n.464+1014C>T		intron	N/A	ENSP00000408788.1
	DONSON	ENST00000444517.5	TSL:1	n.464+1014C>T		intron	N/A	ENSP00000392405.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251458 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461672 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.3
DANN	Benign	0.78
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs779803447; hg19: chr21-34955882;