19-45956707-T-C

Variant names:

• chr19-45956707-T-C
• rs11083790
• NM_002516.4:c.230-2761A>G

Variant summary

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

The NM_002516.4(NOVA2):​c.230-2761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,190 control chromosomes in the GnomAD database, including 41,412 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 0.73 (41412 hom., cov: 33)
• Consequence: NOVA2 NM_002516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 3 publications found

Genes affected

NOVA2 (HGNC:7887): (NOVA alternative splicing regulator 2) Enables sequence-specific mRNA binding activity. Involved in neuron differentiation and regulation of alternative mRNA splicing, via spliceosome. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NOVA2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA2	NM_002516.4	MANE Select	c.230-2761A>G		intron	N/A	NP_002507.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA2	ENST00000263257.6	TSL:1 MANE Select	c.230-2761A>G		intron	N/A	ENSP00000263257.4
	NOVA2	ENST00000676183.1		c.422-2761A>G		intron	N/A	ENSP00000501708.1
	NOVA2	ENST00000596784.1	TSL:3	c.-98-2761A>G		intron	N/A	ENSP00000471736.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111445 AN: 152072 Hom.: 41377 Cov.: 33

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.733 AC: 111530 AN: 152190 Hom.: 41412 Cov.: 33 AF XY: 0.737 AC XY: 54827 AN XY: 74418

African (AFR) AF: 0.622 AC: 25826 AN: 41498

American (AMR) AF: 0.762 AC: 11649 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3468

East Asian (EAS) AF: 0.838 AC: 4330 AN: 5168

South Asian (SAS) AF: 0.653 AC: 3150 AN: 4822

European-Finnish (FIN) AF: 0.885 AC: 9394 AN: 10620

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52229 AN: 68004

Other (OTH) AF: 0.731 AC: 1540 AN: 2108

Alfa AF: 0.759 Hom.: 5505

Bravo AF: 0.723

Asia WGS AF: 0.751 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		-1.9
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: rs11083790; hg19: chr19-46459965;