Genetic Variant AUTS2:p.Leu10Phe (chr7-69599681-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015570.4(AUTS2):c.28C>T(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L10V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AUTS2
NM_015570.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16046533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AUTS2	NM_015570.4	MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 19	NP_056385.1
AUTS2	NM_001127231.3		c.28C>T	p.Leu10Phe	missense	Exon 1 of 18	NP_001120703.1
AUTS2	NM_001127232.3		c.28C>T	p.Leu10Phe	missense	Exon 1 of 5	NP_001120704.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 19	ENSP00000344087.4
AUTS2	ENST00000406775.6	TSL:1	c.28C>T	p.Leu10Phe	missense	Exon 1 of 18	ENSP00000385263.2
AUTS2	ENST00000403018.3	TSL:1	c.28C>T	p.Leu10Phe	missense	Exon 1 of 5	ENSP00000385572.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1174916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

568156

African (AFR)

AF:

0.00

AC:

AN:

23520

American (AMR)

AF:

0.00

AC:

AN:

10228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16172

East Asian (EAS)

AF:

0.00

AC:

AN:

27244

South Asian (SAS)

AF:

0.00

AC:

AN:

36578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

975056

Other (OTH)

AF:

0.00

AC:

AN:

47704

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

PhyloP100

1.2

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.70

REVEL

Benign

0.022

Sift

Pathogenic

0.0

Sift4G

Benign

0.79

Polyphen

0.0080

Vest4

0.16

MutPred

0.33

Loss of catalytic residue at L10 (P = 0.0713)

MVP

0.10

MPC

2.6

ClinPred

0.63

GERP RS

3.6

PromoterAI

-0.0018

Neutral

(source)

Varity_R

0.090

gMVP

0.056

Mutation Taster

=82/18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over