7-69599681-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015570.4(AUTS2):c.28C>G(p.Leu10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15830332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.28C>G	p.Leu10Val	missense_variant	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.28C>G	p.Leu10Val	missense_variant	1/19	1	NM_015570.4	P4
AUTS2	ENST00000406775.6	c.28C>G	p.Leu10Val	missense_variant	1/18	1
AUTS2	ENST00000403018.3	c.28C>G	p.Leu10Val	missense_variant	1/5	1
AUTS2	ENST00000644939.1	c.28C>G	p.Leu10Val	missense_variant	1/19			A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 341828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 183446

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2021

Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.19

T

BayesDel_noAF

Benign

-0.51

Cadd

Uncertain

25

Dann

Uncertain

0.99

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.39

N

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Pathogenic

0.33

D

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

T

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.93

D

Polyphen

0.36

.;B;B;.

Vest4

0.15, 0.18, 0.11

MutPred

0.28

Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);Gain of methylation at K13 (P = 0.1116);

MVP

0.10

MPC

2.3

ClinPred

0.62

D

GERP RS

3.6

Varity_R

0.098

gMVP

0.073

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-69064667;