7-69599759-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015570.4(AUTS2):​c.106G>C​(p.Gly36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,369,464 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

3
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.763
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2022962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AUTS2NM_015570.4 linkc.106G>C p.Gly36Arg missense_variant Exon 1 of 19 ENST00000342771.10 NP_056385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AUTS2ENST00000342771.10 linkc.106G>C p.Gly36Arg missense_variant Exon 1 of 19 1 NM_015570.4 ENSP00000344087.4 Q8WXX7-1

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151546
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
8.21e-7
AC:
1
AN:
1217918
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
594320
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000365
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151546
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74016
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

AUTS2-related disorder Uncertain:1
Apr 16, 2024
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

The AUTS2 c.106G>C variant is predicted to result in the amino acid substitution p.Gly36Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Inborn genetic diseases Uncertain:1
Jun 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.106G>C (p.G36R) alteration is located in exon 1 (coding exon 1) of the AUTS2 gene. This alteration results from a G to C substitution at nucleotide position 106, causing the glycine (G) at amino acid position 36 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
.;.;T;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.65
T;T;T;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
.;N;N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.36
.;N;N;N
REVEL
Benign
0.052
Sift
Uncertain
0.0030
.;D;D;T
Sift4G
Pathogenic
0.0
.;D;D;D
Polyphen
0.021
.;B;B;.
Vest4
0.24, 0.24, 0.23
MutPred
0.45
Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);Gain of methylation at G36 (P = 0.001);
MVP
0.068
MPC
3.1
ClinPred
0.53
D
GERP RS
3.0
Varity_R
0.089
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs934214411; hg19: chr7-69064745; API