rs10237984

Variant names:

• chr7-69833145-G-T
• rs10237984
• NM_015570.4:c.310-66141G>T

Variant summary

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

The NM_015570.4(AUTS2):​c.310-66141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,074 control chromosomes in the GnomAD database, including 2,368 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 0.14 (2368 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.310-66141G>T		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.310-66141G>T		intron	N/A	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.310-66141G>T		intron	N/A	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.310-66141G>T		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.310-66141G>T		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000403018.3	TSL:1	c.310-66141G>T		intron	N/A	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21287 AN: 151956 Hom.: 2367 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.140 AC: 21300 AN: 152074 Hom.: 2368 Cov.: 32 AF XY: 0.148 AC XY: 11007 AN XY: 74320

African (AFR) AF: 0.193 AC: 8014 AN: 41498

American (AMR) AF: 0.208 AC: 3180 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2779 AN: 5156

South Asian (SAS) AF: 0.302 AC: 1450 AN: 4806

European-Finnish (FIN) AF: 0.102 AC: 1078 AN: 10564

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4251 AN: 67990

Other (OTH) AF: 0.127 AC: 267 AN: 2108

Alfa AF: 0.0911 Hom.: 4712

Bravo AF: 0.150

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		0.033
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10237984;

hg19: chr7-69298131;