rs149961458

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015570.4(AUTS2):c.611A>G(p.Glu204Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,594,876 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0024 ( 8 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 6.10

Publications

4 publications found

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]

AUTS2 Gene-Disease associations (from GenCC):

autism spectrum disorder due to AUTS2 deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014653385).

BP6

Variant 7-70118220-A-G is Benign according to our data. Variant chr7-70118220-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00134 (202/150934) while in subpopulation NFE AF = 0.00267 (181/67724). AF 95% confidence interval is 0.00235. There are 2 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.611A>G	p.Glu204Gly	missense_variant	Exon 3 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10 link	c.611A>G	p.Glu204Gly	missense_variant	Exon 3 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

202

AN:

150828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000425

Gnomad FIN

AF:

0.000288

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00267

Gnomad OTH

AF:

0.000485

GnomAD2 exomes

AF:

0.00160

AC:

360

AN:

224908

AF XY:

0.00156

show subpopulations

Gnomad AFR exome

AF:

0.000394

Gnomad AMR exome

AF:

0.000612

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000530

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00237

AC:

3416

AN:

1443942

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1657

AN XY:

718466

show subpopulations

African (AFR)

AF:

0.000220

AC:

AN:

31846

American (AMR)

AF:

0.000525

AC:

AN:

40036

Ashkenazi Jewish (ASJ)

AF:

0.000157

AC:

AN:

25402

East Asian (EAS)

AF:

0.00

AC:

AN:

39234

South Asian (SAS)

AF:

0.000397

AC:

AN:

83090

European-Finnish (FIN)

AF:

0.000790

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.00290

AC:

3204

AN:

1106160

Other (OTH)

AF:

0.00177

AC:

105

AN:

59476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00134

AC:

202

AN:

150934

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

73738

show subpopulations

African (AFR)

AF:

0.000292

AC:

AN:

41112

American (AMR)

AF:

0.000198

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.000425

AC:

AN:

4702

European-Finnish (FIN)

AF:

0.000288

AC:

AN:

10402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00267

AC:

181

AN:

67724

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00131

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00171

AC:

208

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AUTS2: BS1 -

Jan 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autism spectrum disorder due to AUTS2 deficiency

Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AUTS2-related disorder

Benign:1

May 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Sep 01, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

.;.;T;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;D;T;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;L;L;.

PhyloP100

6.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

.;D;N;D;.

REVEL

Benign

0.13

Sift

Uncertain

0.0080

.;D;D;D;.

Sift4G

Benign

0.24

.;T;T;D;.

Polyphen

0.93

.;P;P;.;.

Vest4

0.63, 0.56, 0.75

MVP

0.14

MPC

1.3

ClinPred

0.041

GERP RS

5.3

Varity_R

0.18

gMVP

0.21

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over