Variant 19-45940467-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002516.4(NOVA2):c.875A>C(p.Asn292Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000534 in 1,536,104 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

NOVA2
NM_002516.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.59

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06569046).

BP6

Variant 19-45940467-T-G is Benign according to our data. Variant chr19-45940467-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1298774.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45940467-T-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAdExome at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4 linkuse as main transcript	c.875A>C	p.Asn292Thr	missense_variant	4/4	ENST00000263257.6
NOVA2	XM_006723230.4 linkuse as main transcript	c.548A>C	p.Asn183Thr	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6 linkuse as main transcript	c.875A>C	p.Asn292Thr	missense_variant	4/4	1	NM_002516.4	P1
NOVA2	ENST00000676183.1 linkuse as main transcript	c.1067A>C	p.Asn356Thr	missense_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150570

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:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000994

AC:

AN:

181048

Hom.:

AF XY:

0.000168

AC XY:

AN XY:

101440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000675

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000563

AC:

AN:

1385424

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

688386

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000426

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.000790

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000558

Gnomad4 OTH exome

AF:

0.0000534

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150680

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73636

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:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000101

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.15

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.079

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.65

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.31

REVEL

Benign

0.063

Sift

Benign

0.32

Sift4G

Benign

1.0

Polyphen

0.088

Vest4

0.46

MutPred

0.41

Loss of solvent accessibility (P = 0.0193);

MVP

0.34

ClinPred

0.083

GERP RS

2.2

Varity_R

0.076

gMVP

0.49

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