NM_015570.4:c.2147-1459A>G

Variant names:

• chr7-70783483-A-G
• rs9886351
• NM_015570.4:c.2147-1459A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):​c.2147-1459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,070 control chromosomes in the GnomAD database, including 8,808 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8808 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.2147-1459A>G		intron_variant	Intron 15 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.2147-1459A>G		intron_variant	Intron 15 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50605 AN: 151952 Hom.: 8790 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.296

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.333 AC: 50669 AN: 152070 Hom.: 8808 Cov.: 32 AF XY: 0.336 AC XY: 25005 AN XY: 74340

African (AFR) AF: 0.425 AC: 17620 AN: 41446

American (AMR) AF: 0.288 AC: 4401 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2220 AN: 5172

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4822

European-Finnish (FIN) AF: 0.415 AC: 4388 AN: 10578

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19133 AN: 67980

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.289 Hom.: 29822

Bravo AF: 0.331

Asia WGS AF: 0.359 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.014
DANN	Benign	0.24
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9886351; hg19: chr7-70248469;