chr1-197103126-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_018136.5(ASPM):āc.6125A>Gā(p.Asp2042Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPM | NM_018136.5 | c.6125A>G | p.Asp2042Gly | missense_variant | 18/28 | ENST00000367409.9 | |
ASPM | NM_001206846.2 | c.4066-6962A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPM | ENST00000367409.9 | c.6125A>G | p.Asp2042Gly | missense_variant | 18/28 | 1 | NM_018136.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000981 AC: 149AN: 151928Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000308 AC: 77AN: 249880Hom.: 0 AF XY: 0.000193 AC XY: 26AN XY: 135030
GnomAD4 exome AF: 0.000107 AC: 156AN: 1460788Hom.: 0 Cov.: 41 AF XY: 0.000105 AC XY: 76AN XY: 726722
GnomAD4 genome AF: 0.00100 AC: 152AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.000915 AC XY: 68AN XY: 74344
ClinVar
Submissions by phenotype
Microcephaly 5, primary, autosomal recessive Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 10, 2019 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 29, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 14, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
ASPM-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 19, 2022 | 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