rs7280365

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-33580277-G-A
• chr21-33580277-G-C
• chr21-33580277-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017613.4(DONSON):​c.1351-715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 147,396 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: 𝑓 0.0000068 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00000678 AC: 1 AN: 147396 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000678 AC: 1 AN: 147396 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 71734

African (AFR) AF: 0.0000252 AC: 1 AN: 39644

American (AMR) AF: 0.00 AC: 0 AN: 14770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 4938

South Asian (SAS) AF: 0.00 AC: 0 AN: 4598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66982

Other (OTH) AF: 0.00 AC: 0 AN: 1996

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		0.25

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;