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

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.25

Links

AUTS2 (HGNC:14262):

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 linkuse as main transcript	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 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/19	1	NM_015570.4	P4	Q8WXX7-1
AUTS2	ENST00000406775.6 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/18	1			Q8WXX7-2
AUTS2	ENST00000403018.3 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/5	1			Q8WXX7-3
AUTS2	ENST00000644939.1 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	1/19			A1

Frequencies

GnomAD3 genomes

Cov.:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.053

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.90

D;D;D;D

MetaSVM

Benign

-1.1

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over