19-45940481-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002516.4(NOVA2):c.861A>C(p.Ala287=) variant causes a synonymous change. The variant allele was found at a frequency of 0.701 in 1,530,170 control chromosomes in the GnomAD database, including 378,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39861 hom., cov: 33)
  • Exomes 𝑓: 0.70 (338384 hom.)
• Consequence: NOVA2 NM_002516.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-45940481-T-G is Benign according to our data. Variant chr19-45940481-T-G is described in ClinVar as [Benign]. Clinvar id is 1326984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4	c.861A>C	p.Ala287=	synonymous_variant	4/4	ENST00000263257.6
NOVA2	XM_006723230.4	c.534A>C	p.Ala178=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6	c.861A>C	p.Ala287=	synonymous_variant	4/4	1	NM_002516.4	P1
NOVA2	ENST00000676183.1	c.1053A>C	p.Ala351=	synonymous_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.723 AC: 108776 AN: 150510 Hom.: 39826 Cov.: 33

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.701

GnomAD3 exomes AF: 0.678 AC: 120952 AN: 178450 Hom.: 41864 AF XY: 0.682 AC XY: 68081 AN XY: 99782

Gnomad AFR exome AF: 0.791

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.795

Gnomad SAS exome AF: 0.712

Gnomad FIN exome AF: 0.788

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.668

GnomAD4 exome AF: 0.699 AC: 963682 AN: 1379552 Hom.: 338384 Cov.: 65 AF XY: 0.699 AC XY: 478726 AN XY: 685316

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome AF: 0.723 AC: 108856 AN: 150618 Hom.: 39861 Cov.: 33 AF XY: 0.724 AC XY: 53232 AN XY: 73546

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.704

Alfa AF: 0.691 Hom.: 45591

Bravo AF: 0.714

Asia WGS AF: 0.797 AC: 2490 AN: 3128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.79

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: rs28742045; hg19: chr19-46443739; COSMIC: COSV54355731; COSMIC: COSV54355731;