rs12698902

Variant names:

• chr7-70372333-A-G
• rs12698902
• NM_015570.4:c.661-63419A>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.661-63419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,084 control chromosomes in the GnomAD database, including 9,195 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 (9195 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.661-63419A>G		intron_variant	Intron 4 of 18	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.661-63419A>G		intron_variant	Intron 4 of 18	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50855 AN: 151966 Hom.: 9156 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50945 AN: 152084 Hom.: 9195 Cov.: 32 AF XY: 0.338 AC XY: 25135 AN XY: 74338

African (AFR) AF: 0.467 AC: 19380 AN: 41466

American (AMR) AF: 0.287 AC: 4380 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1022 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5162

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4824

European-Finnish (FIN) AF: 0.363 AC: 3840 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19099 AN: 67982

Other (OTH) AF: 0.304 AC: 642 AN: 2112

Alfa AF: 0.291 Hom.: 20768

Bravo AF: 0.336

Asia WGS AF: 0.276 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.087
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: rs12698902; hg19: chr7-69837319;