7-70790590-GCCACCACCACCACCACCA-GCCACCACCACCA
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_015570.4(AUTS2):c.3395_3400delACCACC(p.His1132_His1133del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000637 in 1,600,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
AUTS2
NM_015570.4 disruptive_inframe_deletion
NM_015570.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.22
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.
BP6
Variant 7-70790590-GCCACCA-G is Benign according to our data. Variant chr7-70790590-GCCACCA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1300716.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr7-70790590-GCCACCA-G is described in Lovd as [Benign].
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| AUTS2 | NM_015570.4 | c.3395_3400delACCACC | p.His1132_His1133del | disruptive_inframe_deletion | 19/19 | ENST00000342771.10 | NP_056385.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| AUTS2 | ENST00000342771.10 | c.3395_3400delACCACC | p.His1132_His1133del | disruptive_inframe_deletion | 19/19 | 1 | NM_015570.4 | ENSP00000344087.4 |
Frequencies
GnomAD3 genomes 0.0000988 AC: 15AN: 151772Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000842 AC: 16AN: 189948Hom.: 0 AF XY: 0.000116 AC XY: 12AN XY: 103280
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GnomAD4 exome AF: 0.0000600 AC: 87AN: 1448934Hom.: 0 AF XY: 0.0000653 AC XY: 47AN XY: 719796
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GnomAD4 genome 0.0000988 AC: 15AN: 151772Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74082
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 12, 2023 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with AUTS2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.3395_3400del, results in the deletion of 2 amino acid(s) of the AUTS2 protein (p.His1132_His1133del), but otherwise preserves the integrity of the reading frame. - |
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2021 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | AUTS2: BS2 - |
Autism spectrum disorder due to AUTS2 deficiency Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at