19-45956707-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4	c.230-2761A>G		intron_variant		ENST00000263257.6
NOVA2	XM_006723230.4	c.-98-2761A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6	c.230-2761A>G		intron_variant		1	NM_002516.4	P1
NOVA2	ENST00000596784.1	c.-98-2761A>G		intron_variant		3
NOVA2	ENST00000676183.1	c.422-2761A>G		intron_variant

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

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.731

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.8
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs11083790; hg19: chr19-46459965;