19-45940394-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002516.4(NOVA2):c.948C>T(p.Ala316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000797 in 1,444,510 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: NOVA2 NM_002516.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 19-45940394-G-A is Benign according to our data. Variant chr19-45940394-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.
• BS2: High AC in GnomAd at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4	c.948C>T	p.Ala316=	synonymous_variant	4/4	ENST00000263257.6
NOVA2	XM_006723230.4	c.621C>T	p.Ala207=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6	c.948C>T	p.Ala316=	synonymous_variant	4/4	1	NM_002516.4	P1
NOVA2	ENST00000676183.1	c.1140C>T	p.Ala380=	synonymous_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.000539 AC: 81 AN: 150260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

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: 0.000951

Gnomad OTH AF: 0.000485

GnomAD3 exomes AF: 0.000376 AC: 36 AN: 95832 Hom.: 0 AF XY: 0.000384 AC XY: 21 AN XY: 54626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000827 AC: 1070 AN: 1294142 Hom.: 0 Cov.: 31 AF XY: 0.000763 AC XY: 488 AN XY: 639296

Gnomad4 AFR exome AF: 0.000196

Gnomad4 AMR exome AF: 0.0000765

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000238

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.000483

GnomAD4 genome AF: 0.000539 AC: 81 AN: 150368 Hom.: 0 Cov.: 32 AF XY: 0.000518 AC XY: 38 AN XY: 73392

Gnomad4 AFR AF: 0.000339

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000951

Gnomad4 OTH AF: 0.000480

Alfa AF: 0.000842 Hom.: 0

Bravo AF: 0.000544

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

NOVA2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	12
Dann	Benign	0.96

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: rs373683710; hg19: chr19-46443652;