7-69599655-T-C
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2_SupportingPP5_Moderate
The NM_015570(AUTS2):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
AUTS2
NM_015570 start_lost
NM_015570 start_lost
Scores
3
1
7
Clinical Significance
Conservation
PhyloP100: 3.25
Links
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_015570 (AUTS2) was described as [Pathogenic] in ClinVar as 1174542
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PP5
?
Variant 7:69599655-T>C is Pathogenic according to our data. Variant chr7-69599655-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1033782. Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUTS2 | NM_015570.4 | c.2T>C | p.Met1? | start_lost | 1/19 | ENST00000342771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUTS2 | ENST00000342771.10 | c.2T>C | p.Met1? | start_lost | 1/19 | 1 | NM_015570.4 | P4 | |
AUTS2 | ENST00000406775.6 | c.2T>C | p.Met1? | start_lost | 1/18 | 1 | |||
AUTS2 | ENST00000403018.3 | c.2T>C | p.Met1? | start_lost | 1/5 | 1 | |||
AUTS2 | ENST00000644939.1 | c.2T>C | p.Met1? | start_lost | 1/19 | A1 |
Frequencies
GnomAD3 genomesCov.: 32
GnomAD3 genomes
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autism spectrum disorder due to AUTS2 deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 23, 2018 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. Defects in AUTS2 are the cause of Mental retardation, autosomal dominant 26 (MRD26) [MIM:615834], an autosomal dominant disorder characterized by intellectual disability, autism, developmental delay, short stature, microcephaly, cerebral palsy, kyphosis, and facial dysmorphisms [PMID 23332918] - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
Polyphen
0.0030
.;B;B;.
Vest4
0.72, 0.70, 0.72
MutPred
Gain of phosphorylation at M1 (P = 0.002);Gain of phosphorylation at M1 (P = 0.002);Gain of phosphorylation at M1 (P = 0.002);Gain of phosphorylation at M1 (P = 0.002);
MVP
0.52
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at