rs761447719
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_018136.5(ASPM):c.2T>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ASPM
NM_018136.5 start_lost
NM_018136.5 start_lost
Scores
4
5
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.04
Publications
0 publications found
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 recessiveInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- autosomal recessive primary microcephalyInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 11 pathogenic variants. Next in-frame start position is after 122 codons. Genomic position: 197144034. Lost 0.035 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455042Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3AN XY: 723770 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1455042
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
723770
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33396
American (AMR)
AF:
AC:
0
AN:
44652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26072
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
3
AN:
86156
European-Finnish (FIN)
AF:
AC:
0
AN:
49008
Middle Eastern (MID)
AF:
AC:
0
AN:
4446
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111476
Other (OTH)
AF:
AC:
0
AN:
60162
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.408
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
PhyloP100
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of methylation at M1 (P = 0.0158);Gain of methylation at M1 (P = 0.0158);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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