rs144049904
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_018136.5(ASPM):c.1717C>T(p.Arg573Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,904 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018136.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00208 AC: 317AN: 152070Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00190 AC: 476AN: 251182Hom.: 1 AF XY: 0.00169 AC XY: 230AN XY: 135796
GnomAD4 exome AF: 0.00260 AC: 3804AN: 1461716Hom.: 12 Cov.: 33 AF XY: 0.00250 AC XY: 1819AN XY: 727158
GnomAD4 genome AF: 0.00208 AC: 317AN: 152188Hom.: 1 Cov.: 33 AF XY: 0.00202 AC XY: 150AN XY: 74408
ClinVar
Submissions by phenotype
not specified Benign:3
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not provided Benign:3
ASPM: BP4, BS2 -
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Microcephaly 5, primary, autosomal recessive Uncertain:1
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
ASPM-related disorder Benign:1
This variant is classified as likely 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