GeneBe

1-197084431-TAAAA-TAAAAAA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_018136.5(ASPM):​c.10332-7_10332-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0084 ( 0 hom. )

Consequence

ASPM
NM_018136.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.439

Publications

4 publications found
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 Gene-Disease associations (from GenCC):
  • microcephaly 5, primary, autosomal recessive
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • autosomal recessive primary microcephaly
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00051 (73/143272) while in subpopulation EAS AF = 0.00285 (14/4918). AF 95% confidence interval is 0.00172. There are 0 homozygotes in GnomAd4. There are 40 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASPMNM_018136.5 linkc.10332-7_10332-6dupTT splice_region_variant, intron_variant Intron 27 of 27 ENST00000367409.9 NP_060606.3 Q8IZT6-1B3KWI2
ASPMNM_001206846.2 linkc.5577-7_5577-6dupTT splice_region_variant, intron_variant Intron 26 of 26 NP_001193775.1 Q8IZT6-2B3KWI2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASPMENST00000367409.9 linkc.10332-6_10332-5insTT splice_region_variant, intron_variant Intron 27 of 27 1 NM_018136.5 ENSP00000356379.4 Q8IZT6-1

Frequencies

GnomAD3 genomes
AF:
0.000496
AC:
71
AN:
143214
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000259
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000280
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00284
Gnomad SAS
AF:
0.000664
Gnomad FIN
AF:
0.000799
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000625
Gnomad OTH
AF:
0.000514
GnomAD2 exomes
AF:
0.00452
AC:
784
AN:
173358
AF XY:
0.00457
show subpopulations
Gnomad AFR exome
AF:
0.00207
Gnomad AMR exome
AF:
0.00231
Gnomad ASJ exome
AF:
0.00326
Gnomad EAS exome
AF:
0.00267
Gnomad FIN exome
AF:
0.00716
Gnomad NFE exome
AF:
0.00583
Gnomad OTH exome
AF:
0.00394
GnomAD4 exome
AF:
0.00840
AC:
10593
AN:
1261552
Hom.:
0
Cov.:
0
AF XY:
0.00791
AC XY:
5013
AN XY:
634116
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00299
AC:
87
AN:
29116
American (AMR)
AF:
0.00235
AC:
96
AN:
40768
Ashkenazi Jewish (ASJ)
AF:
0.00495
AC:
120
AN:
24256
East Asian (EAS)
AF:
0.00637
AC:
238
AN:
37354
South Asian (SAS)
AF:
0.00330
AC:
260
AN:
78774
European-Finnish (FIN)
AF:
0.00409
AC:
181
AN:
44290
Middle Eastern (MID)
AF:
0.00618
AC:
31
AN:
5020
European-Non Finnish (NFE)
AF:
0.00972
AC:
9224
AN:
948530
Other (OTH)
AF:
0.00666
AC:
356
AN:
53444
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.285
Heterozygous variant carriers
0
876
1751
2627
3502
4378
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
434
868
1302
1736
2170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000510
AC:
73
AN:
143272
Hom.:
0
Cov.:
0
AF XY:
0.000576
AC XY:
40
AN XY:
69412
show subpopulations
African (AFR)
AF:
0.0000258
AC:
1
AN:
38714
American (AMR)
AF:
0.000280
AC:
4
AN:
14306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3364
East Asian (EAS)
AF:
0.00285
AC:
14
AN:
4918
South Asian (SAS)
AF:
0.000888
AC:
4
AN:
4502
European-Finnish (FIN)
AF:
0.000799
AC:
7
AN:
8764
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
286
European-Non Finnish (NFE)
AF:
0.000625
AC:
41
AN:
65568
Other (OTH)
AF:
0.00102
AC:
2
AN:
1964
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.444
Heterozygous variant carriers
0
4
8
12
16
20
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00452
Hom.:
495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.44
Mutation Taster
=99/1
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs200839523; hg19: chr1-197053561; API