NM_017613.4(DONSON):c.1375_1376del (p.Gln459fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003707370.2

Allele description [Variation Report for NM_017613.4(DONSON):c.1375_1376del (p.Gln459fs)]

NM_017613.4(DONSON):c.1375_1376del (p.Gln459fs)

Gene:

DONSON:DNA replication fork stabilization factor DONSON [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

21q22.11

Genomic location:

Preferred name:

NM_017613.4(DONSON):c.1375_1376del (p.Gln459fs)

HGVS:

NC_000021.9:g.33579538GT[1]
NM_017613.4:c.1375_1376delMANE SELECT
NP_060083.1:p.Gln459fs
NC_000021.8:g.34951843_34951844del
NC_000021.8:g.34951844GT[1]

Protein change:

Q459fs

Molecular consequence:

NM_017613.4:c.1375_1376del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004477951	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28191891, 28630177, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004477951

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

Reynolds JJ, Bicknell LS, Carroll P, Higgs MR, Shaheen R, Murray JE, Papadopoulos DK, Leitch A, Murina O, Tarnauskaitė Ž, Wessel SR, Zlatanou A, Vernet A, von Kriegsheim A, Mottram RM, Logan CV, Bye H, Li Y, Brean A, Maddirevula S, Challis RC, Skouloudaki K, et al.

Nat Genet. 2017 Apr;49(4):537-549. doi: 10.1038/ng.3790. Epub 2017 Feb 13.

PubMed [citation]

PMID:: 28191891
PMCID:: PMC5450907

Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome.

Evrony GD, Cordero DR, Shen J, Partlow JN, Yu TW, Rodin RE, Hill RS, Coulter ME, Lam AN, Jayaraman D, Gerrelli D, Diaz DG, Santos C, Morrison V, Galli A, Tschulena U, Wiemann S, Martel MJ, Spooner B, Ryu SC, Elhosary PC, Richardson JM, et al.

Genome Res. 2017 Aug;27(8):1323-1335. doi: 10.1101/gr.219899.116. Epub 2017 Jun 19.

PubMed [citation]

PMID:: 28630177
PMCID:: PMC5538549

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004477951.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with DONSON-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs775673237, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Gln459Serfs*10) in the DONSON gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DONSON are known to be pathogenic (PMID: 28191891, 28630177).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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