rs1792260350

Variant names:

• chr7-69599681-C-G
• rs1792260350
• NM_015570.4:c.28C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-69599681-C-G
• chr7-69599681-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. The variant was absent in control chromosomes in GnomAD project. 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
• Publications: 0 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: 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=0.15830332).

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.28C>G	p.Leu10Val	missense	Exon 1 of 19	NP_056385.1
	AUTS2	NM_001127231.3		c.28C>G	p.Leu10Val	missense	Exon 1 of 18	NP_001120703.1
	AUTS2	NM_001127232.3		c.28C>G	p.Leu10Val	missense	Exon 1 of 5	NP_001120704.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.28C>G	p.Leu10Val	missense	Exon 1 of 19	ENSP00000344087.4
	AUTS2	ENST00000406775.6	TSL:1	c.28C>G	p.Leu10Val	missense	Exon 1 of 18	ENSP00000385263.2
	AUTS2	ENST00000403018.3	TSL:1	c.28C>G	p.Leu10Val	missense	Exon 1 of 5	ENSP00000385572.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1174916 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 568156

African (AFR) AF: 0.00 AC: 0 AN: 23520

American (AMR) AF: 0.00 AC: 0 AN: 10228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16172

East Asian (EAS) AF: 0.00 AC: 0 AN: 27244

South Asian (SAS) AF: 0.00 AC: 0 AN: 36578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3206

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 975056

Other (OTH) AF: 0.00 AC: 0 AN: 47704

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.032
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.75	T
Polyphen		0.36	B
Vest4		0.15
MutPred		0.28		Gain of methylation at K13 (P = 0.1116)
MVP		0.10
MPC		2.3
ClinPred		0.62	D
GERP RS		3.6
PromoterAI		0.017	Neutral
Varity_R		0.098
gMVP		0.073
Mutation Taster		=84/16	polymorphism

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: rs1792260350; hg19: chr7-69064667;