7-70763034-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015570.4(AUTS2):c.907G>T(p.Ala303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 1,613,978 control chromosomes in the GnomAD database, including 2,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 559 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1987 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0920

Publications

21 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=0.0015388131).

BP6

Variant 7-70763034-G-T is Benign according to our data. Variant chr7-70763034-G-T is described in ClinVar as [Benign]. Clinvar id is 1253894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.907G>T	p.Ala303Ser	missense_variant	Exon 7 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.907G>T	p.Ala303Ser	missense_variant	Exon 7 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.0730

AC:

11094

AN:

151982

Hom.:

557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0754

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.00519

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0387

Gnomad OTH

AF:

0.0892

GnomAD2 exomes

AF:

0.0536

AC:

13469

AN:

251406

AF XY:

0.0530

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0378

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0739

Gnomad FIN exome

AF:

0.00633

Gnomad NFE exome

AF:

0.0410

Gnomad OTH exome

AF:

0.0629

GnomAD4 exome

AF:

0.0462

AC:

67525

AN:

1461876

Hom.:

1987

Cov.:

AF XY:

0.0467

AC XY:

33990

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.150

AC:

5012

AN:

33480

American (AMR)

AF:

0.0405

AC:

1813

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2680

AN:

26136

East Asian (EAS)

AF:

0.0602

AC:

2390

AN:

39700

South Asian (SAS)

AF:

0.0733

AC:

6319

AN:

86256

European-Finnish (FIN)

AF:

0.00698

AC:

373

AN:

53408

Middle Eastern (MID)

AF:

0.119

AC:

688

AN:

5768

European-Non Finnish (NFE)

AF:

0.0402

AC:

44655

AN:

1112008

Other (OTH)

AF:

0.0595

AC:

3595

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4645

9290

13936

18581

23226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1820

3640

5460

7280

9100

<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:

0.0730

AC:

11109

AN:

152102

Hom.:

559

Cov.:

AF XY:

0.0704

AC XY:

5239

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.149

AC:

6159

AN:

41448

American (AMR)

AF:

0.0546

AC:

835

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

380

AN:

3472

East Asian (EAS)

AF:

0.0755

AC:

389

AN:

5152

South Asian (SAS)

AF:

0.0716

AC:

345

AN:

4818

European-Finnish (FIN)

AF:

0.00519

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0387

AC:

2629

AN:

68006

Other (OTH)

AF:

0.0882

AC:

186

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

510

1020

1531

2041

2551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0524

Hom.:

1174

Bravo

AF:

0.0803

TwinsUK

AF:

0.0413

AC:

153

ALSPAC

AF:

0.0472

AC:

182

ESP6500AA

AF:

0.143

AC:

629

ESP6500EA

AF:

0.0455

AC:

391

ExAC

AF:

0.0547

AC:

6643

Asia WGS

AF:

0.0760

AC:

262

AN:

3478

EpiCase

AF:

0.0507

EpiControl

AF:

0.0486

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.4

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.017

.;.;T;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.67

T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

.;N;N;.;.

PhyloP100

0.092

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.15

.;N;N;.;.

REVEL

Benign

0.035

Sift

Benign

0.27

.;T;T;.;.

Sift4G

Benign

0.69

.;T;T;T;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.057, 0.038

MPC

0.39

ClinPred

0.0012

GERP RS

1.5

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.12

gMVP

0.084

Mutation Taster

=98/2

polymorphism (auto)

(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