Variant chr19-45940255-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002516.4(NOVA2):c.1087A>T(p.Asn363Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 146,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOVA2
NM_002516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3894005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOVA2	NM_002516.4 linkuse as main transcript	c.1087A>T	p.Asn363Tyr	missense_variant	4/4	ENST00000263257.6	NP_002507.1	Q9UNW9
NOVA2	XM_006723230.4 linkuse as main transcript	c.760A>T	p.Asn254Tyr	missense_variant	5/5		XP_006723293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOVA2	ENST00000263257.6 linkuse as main transcript	c.1087A>T	p.Asn363Tyr	missense_variant	4/4	1	NM_002516.4	ENSP00000263257.4		Q9UNW9
NOVA2	ENST00000676183.1 linkuse as main transcript	c.1279A>T	p.Asn427Tyr	missense_variant	4/4			ENSP00000501708.1		A0A6Q8PFC2

Frequencies

GnomAD3 genomes

AF:

0.00000683

AC:

AN:

146390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

942978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

444880

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000683

AC:

AN:

146390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71220

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.98

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.45

MutPred

0.35

Gain of helix (P = 0.0496);

MVP

0.47

ClinPred

0.82

GERP RS

3.6

Varity_R

0.12

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over