rs113325473
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_018136.5(ASPM):āc.5741A>Gā(p.Gln1914Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,613,222 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1914H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018136.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.5741A>G | p.Gln1914Arg | missense_variant | 18/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.4066-7346A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.5741A>G | p.Gln1914Arg | missense_variant | 18/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00390 AC: 592AN: 151932Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000927 AC: 232AN: 250378Hom.: 0 AF XY: 0.000628 AC XY: 85AN XY: 135328
GnomAD4 exome AF: 0.000357 AC: 521AN: 1461172Hom.: 3 Cov.: 38 AF XY: 0.000308 AC XY: 224AN XY: 726904
GnomAD4 genome AF: 0.00396 AC: 602AN: 152050Hom.: 1 Cov.: 32 AF XY: 0.00371 AC XY: 276AN XY: 74336
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 19, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Microcephaly 5, primary, autosomal recessive Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 08, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 01, 2018 | - - |
ASPM-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 30, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at