NM_018136.5(ASPM):c.1729_1730del (p.Ser577fs) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 24, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000483372.8

Allele description

NM_018136.5(ASPM):c.1729_1730del (p.Ser577fs)

Gene:
ASPM:assembly factor for spindle microtubules [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
1q31.3
Genomic location:
Preferred name:
NM_018136.5(ASPM):c.1729_1730del (p.Ser577fs)
HGVS:
  • NC_000001.11:g.197142522CT[1]
  • NG_015867.1:g.9170AG[1]
  • NM_001206846.2:c.1729_1730del
  • NM_018136.5:c.1729_1730delMANE SELECT
  • NP_001193775.1:p.Ser577fs
  • NP_060606.3:p.Ser577fs
  • NC_000001.10:g.197111652CT[1]
  • NC_000001.10:g.197111652_197111653del
  • NM_018136.4:c.1727_1728delAG
  • NM_018136.4:c.1729_1730delAG
Protein change:
S577fs
Links:
dbSNP: rs199422146
NCBI 1000 Genomes Browser:
rs199422146
Molecular consequence:
  • NM_001206846.2:c.1729_1730del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_018136.5:c.1729_1730del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000566012GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Pathogenic
(Mar 27, 2020) 		germlineclinical testing

Citation Link,

SCV002219520Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 24, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Protein-truncating mutations in ASPM cause variable reduction in brain size.

Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG.

Am J Hum Genet. 2003 Nov;73(5):1170-7. Epub 2003 Oct 21.

PubMed [citation]
PMID:
14574646
PMCID:
PMC1180496

The molecular landscape of ASPM mutations in primary microcephaly.

Nicholas AK, Swanson EA, Cox JJ, Karbani G, Malik S, Springell K, Hampshire D, Ahmed M, Bond J, Di Benedetto D, Fichera M, Romano C, Dobyns WB, Woods CG.

J Med Genet. 2009 Apr;46(4):249-53. doi: 10.1136/jmg.2008.062380. Epub 2008 Nov 21.

PubMed [citation]
PMID:
19028728
PMCID:
PMC2658750
See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000566012.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 14574646, 31589614)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002219520.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

ClinVar contains an entry for this variant (Variation ID: 402179). This variant is also known as c.1727delAG. This premature translational stop signal has been observed in individual(s) with primary microcephaly (PMID: 14574646). This variant is present in population databases (rs747238090, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Ser577Argfs*33) in the ASPM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASPM are known to be pathogenic (PMID: 19028728, 23611254). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024