19-45940193-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002516.4(NOVA2):c.1149C>T(p.Ala383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 1,552,094 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (3 hom.)
• Consequence: NOVA2 NM_002516.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.139

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-45940193-G-A is Benign according to our data. Variant chr19-45940193-G-A is described in ClinVar as [Benign]. Clinvar id is 788023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.139 with no splicing effect.
• BS2: High AC in GnomAd at 493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4	c.1149C>T	p.Ala383=	synonymous_variant	4/4	ENST00000263257.6
NOVA2	XM_006723230.4	c.822C>T	p.Ala274=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6	c.1149C>T	p.Ala383=	synonymous_variant	4/4	1	NM_002516.4	P1
NOVA2	ENST00000676183.1	c.1341C>T	p.Ala447=	synonymous_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 493 AN: 148830 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000801

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00196

GnomAD3 exomes AF: 0.000928 AC: 165 AN: 177716 Hom.: 1 AF XY: 0.000711 AC XY: 72 AN XY: 101306

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000845

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.000490 AC: 687 AN: 1403160 Hom.: 3 Cov.: 31 AF XY: 0.000434 AC XY: 303 AN XY: 698010

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.000676

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000567

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.000316

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.000969

GnomAD4 genome AF: 0.00331 AC: 493 AN: 148934 Hom.: 4 Cov.: 32 AF XY: 0.00299 AC XY: 217 AN XY: 72566

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.000800

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.000225

Gnomad4 OTH AF: 0.00194

Alfa AF: 0.00158 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	NOVA2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.4
Dann	Benign	0.94

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: rs372234470; hg19: chr19-46443451; COSMIC: COSV99611096; COSMIC: COSV99611096;