Genetic Variant NOVA2:c.*2821T>C (chr19-45937042-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002516.4(NOVA2):c.*2821T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,980 control chromosomes in the GnomAD database, including 24,084 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 0.55 ( 24080 hom., cov: 30)

Exomes 𝑓: 0.44 ( 4 hom. )

Consequence

NOVA2
NM_002516.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.239

Publications

4 publications found

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 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

NOVA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOVA2	NM_002516.4 link	c.*2821T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000263257.6	NP_002507.1	Q9UNW9
NOVA2	XM_006723230.4 link	c.*2821T>C		3_prime_UTR_variant	Exon 5 of 5		XP_006723293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOVA2	ENST00000263257.6 link	c.*2821T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_002516.4	ENSP00000263257.4		Q9UNW9
NOVA2	ENST00000676183.1 link	c.*2821T>C		3_prime_UTR_variant	Exon 4 of 4			ENSP00000501708.1		A0A6Q8PFC2

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84270

AN:

151828

Hom.:

24070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.645

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.526

GnomAD4 exome

AF:

0.441

AC:

AN:

Hom.:

Cov.:

AF XY:

0.409

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.375

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.555

AC:

84307

AN:

151946

Hom.:

24080

Cov.:

AF XY:

0.558

AC XY:

41450

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.460

AC:

19074

AN:

41424

American (AMR)

AF:

0.431

AC:

6582

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1962

AN:

3472

East Asian (EAS)

AF:

0.644

AC:

3329

AN:

5166

South Asian (SAS)

AF:

0.644

AC:

3097

AN:

4810

European-Finnish (FIN)

AF:

0.743

AC:

7857

AN:

10576

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.598

AC:

40650

AN:

67926

Other (OTH)

AF:

0.530

AC:

1119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1857

3713

5570

7426

9283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.573

Hom.:

48867

Bravo

AF:

0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.3

(source)

DANN

Benign

0.76

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over