7-69599664-C-T

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.11C>T(p.Pro4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0046 in 1,304,368 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 22 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.82

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 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=0.0038175583).

BP6

Variant 7-69599664-C-T is Benign according to our data. Variant chr7-69599664-C-T is described in ClinVar as [Benign]. Clinvar id is 975656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-69599664-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00289 (440/152146) while in subpopulation NFE AF = 0.00512 (348/67966). AF 95% confidence interval is 0.00468. There are 2 homozygotes in GnomAd4. There are 177 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 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.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00341

AC:

AN:

11154

AF XY:

0.00368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000211

Gnomad NFE exome

AF:

0.00609

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.00483

AC:

5563

AN:

1152222

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

2610

AN XY:

554422

show subpopulations

Gnomad4 AFR exome

AF:

0.000990

AC:

AN:

23236

Gnomad4 AMR exome

AF:

0.00197

AC:

AN:

9142

Gnomad4 ASJ exome

AF:

0.00533

AC:

AN:

15394

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

27018

Gnomad4 SAS exome

AF:

0.000280

AC:

AN:

32142

Gnomad4 FIN exome

AF:

0.000544

AC:

AN:

33080

Gnomad4 NFE exome

AF:

0.00546

AC:

5256

AN:

962466

Gnomad4 Remaining exome

AF:

0.00335

AC:

156

AN:

46632

Heterozygous variant carriers

307

615

922

1230

1537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<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:

0.00289

AC:

440

AN:

152146

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000842

AC:

0.000842399

AN:

0.000842399

Gnomad4 AMR

AF:

0.00124

AC:

0.00124134

AN:

0.00124134

Gnomad4 ASJ

AF:

0.00548

AC:

0.00547866

AN:

0.00547866

Gnomad4 EAS

AF:

0.000196

AC:

0.000195848

AN:

0.000195848

Gnomad4 SAS

AF:

0.000414

AC:

0.000414079

AN:

0.000414079

Gnomad4 FIN

AF:

0.000660

AC:

0.000659631

AN:

0.000659631

Gnomad4 NFE

AF:

0.00512

AC:

0.00512021

AN:

0.00512021

Gnomad4 OTH

AF:

0.00380

AC:

0.00379867

AN:

0.00379867

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00390

Hom.:

Bravo

AF:

0.00296

ExAC

AF:

0.000722

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Mar 21, 2023

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant has been identified by standard clinical testing. -

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AUTS2: BS1, BS2 -

Nov 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AUTS2-related disorder

Benign:1

Jul 10, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Intellectual disability

Benign:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

.;.;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

.;L;L;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.93

.;N;N;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Uncertain

0.010

.;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.38, 0.37, 0.47

MVP

0.47

MPC

2.6

ClinPred

0.067

GERP RS

3.6

Varity_R

0.25

gMVP

0.16

Mutation Taster

=89/11

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over