rs35744709
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001605.3(AARS1):c.2900A>T(p.Lys967Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,614,088 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K967N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001605.3 missense
Scores
Clinical Significance
Conservation
Publications
- Charcot-Marie-Tooth disease axonal type 2NInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
- undetermined early-onset epileptic encephalopathyInheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
- developmental and epileptic encephalopathy, 29Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- trichothiodystrophy 8, nonphotosensitiveInheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00942 AC: 1433AN: 152202Hom.: 10 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00992 AC: 2493AN: 251344 AF XY: 0.00994 show subpopulations
GnomAD4 exome AF: 0.0123 AC: 17971AN: 1461768Hom.: 147 Cov.: 31 AF XY: 0.0120 AC XY: 8758AN XY: 727200 show subpopulations
GnomAD4 genome AF: 0.00941 AC: 1433AN: 152320Hom.: 10 Cov.: 33 AF XY: 0.00940 AC XY: 700AN XY: 74474 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:4
AARS1: BS1, BS2 -
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Charcot-Marie-Tooth disease axonal type 2N Benign:2
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not specified Benign:1
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Charcot-Marie-Tooth disease type 2 Benign:1
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Charcot-Marie-Tooth disease axonal type 2N;C4225361:Developmental and epileptic encephalopathy, 29;C5562044:Leukoencephalopathy, hereditary diffuse, with spheroids 2;C5562057:Trichothiodystrophy 8, nonphotosensitive Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at