NM_018136.5(ASPM):c.8191_8192del (p.Glu2731fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 20, 2023
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:: RCV002513151.4

Allele description [Variation Report for NM_018136.5(ASPM):c.8191_8192del (p.Glu2731fs)]

NM_018136.5(ASPM):c.8191_8192del (p.Glu2731fs)

Gene:

ASPM:assembly factor for spindle microtubules [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_018136.5(ASPM):c.8191_8192del (p.Glu2731fs)

HGVS:

NC_000001.11:g.197101060_197101061del
NG_015867.1:g.50635_50636del
NM_001206846.2:c.4066-4896_4066-4895del
NM_018136.4:c.8191_8192del
NM_018136.5:c.8191_8192delMANE SELECT
NP_060606.3:p.Glu2731fs
NC_000001.10:g.197070189_197070190del
NC_000001.10:g.197070190_197070191del
NM_018136.4:c.8190_8191delAG

Protein change:

E2731fs

Links:

dbSNP: rs199422177

NCBI 1000 Genomes Browser:

rs199422177

Molecular consequence:

NM_018136.5:c.8191_8192del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206846.2:c.4066-4896_4066-4895del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens long intergenic non-protein coding RNA 2522 (LINC02522), transcript...
Homo sapiens long intergenic non-protein coding RNA 2522 (LINC02522), transcript variant 7, long non-coding RNA
gi|2428898175|ref|NR_183338.1|

Nucleotide
Homo sapiens uncharacterized LOC101927759 (LOC101927759), long non-coding RNA
Homo sapiens uncharacterized LOC101927759 (LOC101927759), long non-coding RNA
gi|1315690869|ref|NR_152848.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523939	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19770472, 19028728, 23611254, 28492532
SCV005201679	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 20, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523939

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2022)

germline

clinical testing

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

SCV005201679

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 20, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations.

Passemard S, Titomanlio L, Elmaleh M, Afenjar A, Alessandri JL, Andria G, de Villemeur TB, Boespflug-Tanguy O, Burglen L, Del Giudice E, Guimiot F, Hyon C, Isidor B, Mégarbané A, Moog U, Odent S, Hernandez K, Pouvreau N, Scala I, Schaer M, Gressens P, Gerard B, et al.

Neurology. 2009 Sep 22;73(12):962-9. doi: 10.1212/WNL.0b013e3181b8799a.

PubMed [citation]

PMID:: 19770472

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003523939.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This premature translational stop signal has been observed in individual(s) with primary microcephaly (PMID: 19770472). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 21613). This variant is also known as c. 8190_8191delAG (p.Glu2731LysfsX18*). This variant is present in population databases (rs773874006, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu2731Lysfs*19) 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).

#	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

From GeneDx, SCV005201679.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 19770472)

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

Last Updated: Sep 29, 2024

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