dbSNP rs771592016: NOVA2:p.Ala323_Ala324del (chr19-45940369-TGGCGGC-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_002516.4(NOVA2):c.967_972delGCCGCC(p.Ala323_Ala324del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000215 in 1,395,792 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

NOVA2
NM_002516.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.88

Publications

0 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):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

NOVA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_002516.4.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA2	NM_002516.4	MANE Select	c.967_972delGCCGCC	p.Ala323_Ala324del	conservative_inframe_deletion	Exon 4 of 4	NP_002507.1	Q9UNW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA2	ENST00000263257.6	TSL:1 MANE Select	c.967_972delGCCGCC	p.Ala323_Ala324del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000263257.4	Q9UNW9
	NOVA2	ENST00000676183.1		c.1159_1164delGCCGCC	p.Ala387_Ala388del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000501708.1	A0A6Q8PFC2

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000160

AC:

AN:

1246278

Hom.:

AF XY:

0.00000163

AC XY:

AN XY:

614456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24424

American (AMR)

AF:

0.00

AC:

AN:

21232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19636

East Asian (EAS)

AF:

0.00

AC:

AN:

23522

South Asian (SAS)

AF:

0.00

AC:

AN:

67040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4496

European-Non Finnish (NFE)

AF:

0.00000100

AC:

AN:

1000114

Other (OTH)

AF:

0.0000203

AC:

AN:

49348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000669

AC:

AN:

149514

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41086

American (AMR)

AF:

0.0000666

AC:

AN:

15010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67078

Other (OTH)

AF:

0.00

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.9

Mutation Taster

=146/54

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over