7-69599717-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_015570.4(AUTS2):c.64C>T(p.Arg22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,173,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
AUTS2
NM_015570.4 missense
NM_015570.4 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 1.82
Genes affected
AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.39417452).
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.64C>T | p.Arg22Trp | missense_variant | Exon 1 of 19 | ENST00000342771.10 | NP_056385.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.64C>T | p.Arg22Trp | missense_variant | Exon 1 of 19 | 1 | NM_015570.4 | ENSP00000344087.4 | ||
AUTS2 | ENST00000406775.6 | c.64C>T | p.Arg22Trp | missense_variant | Exon 1 of 18 | 1 | ENSP00000385263.2 | |||
AUTS2 | ENST00000403018.3 | c.64C>T | p.Arg22Trp | missense_variant | Exon 1 of 5 | 1 | ENSP00000385572.2 | |||
AUTS2 | ENST00000644939.1 | c.64C>T | p.Arg22Trp | missense_variant | Exon 1 of 19 | ENSP00000496726.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000111 AC: 13AN: 1173092Hom.: 0 Cov.: 32 AF XY: 0.00000881 AC XY: 5AN XY: 567314
GnomAD4 exome
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13
AN:
1173092
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32
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AC XY:
5
AN XY:
567314
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2024 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 22 of the AUTS2 protein (p.Arg22Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AUTS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1205753). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;L
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;N;D
REVEL
Benign
Sift
Pathogenic
.;D;D;D
Sift4G
Pathogenic
.;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
0.28, 0.28, 0.47
MutPred
Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);Loss of methylation at R27 (P = 0.0258);
MVP
0.29
MPC
2.6
ClinPred
D
GERP RS
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