dbSNP rs1554489424: AUTS2:p.Leu1207Pro (chr7-70790836-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015570.4(AUTS2):c.3620T>C(p.Leu1207Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 5.77

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4 link	c.3620T>C	p.Leu1207Pro	missense_variant	Exon 19 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.3620T>C	p.Leu1207Pro	missense_variant	Exon 19 of 19	1	NM_015570.4	ENSP00000344087.4		Q8WXX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454964

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

44260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25636

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108198

Other (OTH)

AF:

0.0000167

AC:

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AUTS2-related disorder

Uncertain:1

May 02, 2024

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The AUTS2 c.3620T>C variant is predicted to result in the amino acid substitution p.Leu1207Pro. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Inborn genetic diseases

Uncertain:1

May 22, 2017

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;T;.;.;.;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

T;D;T;D;D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

.;.;L;.;.;.;.

PhyloP100

5.8

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.9

.;D;D;.;.;.;.

REVEL

Benign

0.18

Sift

Uncertain

0.0020

.;D;D;.;.;.;.

Sift4G

Uncertain

0.0090

.;D;D;.;.;D;D

Polyphen

1.0

.;D;D;.;.;.;.

Vest4

0.83, 0.81

MutPred

0.24

.;.;Loss of stability (P = 0.0126);.;.;.;.;

MVP

0.25

MPC

1.5

ClinPred

0.94

GERP RS

4.9

Varity_R

0.61

gMVP

0.47

Mutation Taster

=43/57

disease causing

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over