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GeneBe

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

Scores

3
1
7

Clinical Significance

Pathogenic criteria provided, single submitter P:1

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
AUTS2NM_015570.4 linkuse as main transcriptc.2T>C p.Met1? start_lost 1/19 ENST00000342771.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.2T>C p.Met1? start_lost 1/191 NM_015570.4 P4Q8WXX7-1
AUTS2ENST00000406775.6 linkuse as main transcriptc.2T>C p.Met1? start_lost 1/181 Q8WXX7-2
AUTS2ENST00000403018.3 linkuse as main transcriptc.2T>C p.Met1? start_lost 1/51 Q8WXX7-3
AUTS2ENST00000644939.1 linkuse as main transcriptc.2T>C p.Met1? start_lost 1/19 A1

Frequencies

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 submitterclinical testingBaylor GeneticsApr 23, 2018This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Benign
-0.18
Cadd
Benign
23
Dann
Benign
0.96
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Pathogenic
0.95
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D
Polyphen
0.0030
.;B;B;.
Vest4
0.72, 0.70, 0.72
MutPred
0.77
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
0.99
D
GERP RS
3.6
Varity_R
0.80
gMVP
0.18

Splicing

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: rs1792258600; hg19: chr7-69064641;