rs17550662

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018136.5(ASPM):c.1977T>C(p.Ile659Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 1,611,814 control chromosomes in the GnomAD database, including 2,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 178 hom., cov: 33)

Exomes 𝑓: 0.054 ( 2545 hom. )

Consequence

ASPM
NM_018136.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ASPM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-197139816-A-G is Benign according to our data. Variant chr1-197139816-A-G is described in ClinVar as [Benign]. Clinvar id is 21561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197139816-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5 link	c.1977T>C	p.Ile659Ile	synonymous_variant	Exon 4 of 28	ENST00000367409.9	NP_060606.3	Q8IZT6-1B3KWI2
ASPM	NM_001206846.2 link	c.1977T>C	p.Ile659Ile	synonymous_variant	Exon 4 of 27		NP_001193775.1	Q8IZT6-2B3KWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 link	c.1977T>C	p.Ile659Ile	synonymous_variant	Exon 4 of 28	1	NM_018136.5	ENSP00000356379.4		Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6236

AN:

152176

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00902

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0614

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0632

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0636

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0444

AC:

11155

AN:

251442

Hom.:

336

AF XY:

0.0452

AC XY:

6146

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0589

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0741

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0543

AC:

79216

AN:

1459520

Hom.:

2545

Cov.:

AF XY:

0.0533

AC XY:

38730

AN XY:

726170

show subpopulations

Gnomad4 AFR exome

AF:

0.00763

Gnomad4 AMR exome

AF:

0.0233

Gnomad4 ASJ exome

AF:

0.0621

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0789

Gnomad4 NFE exome

AF:

0.0612

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.0409

AC:

6236

AN:

152294

Hom.:

178

Cov.:

AF XY:

0.0392

AC XY:

2916

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00902

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.0614

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0632

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0559

Hom.:

169

Bravo

AF:

0.0380

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0643

EpiControl

AF:

0.0683

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly 5, primary, autosomal recessive

Benign:2Other:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.3

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over