19-45940369-TGGC-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM4_Supporting BP6_Moderate

The NM_002516.4(NOVA2):c.970_972del(p.Ala324del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000261 in 1,392,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: NOVA2 NM_002516.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.96

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 Likely_benign. Variant got -1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002516.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 19-45940369-TGGC-T is Benign according to our data. Variant chr19-45940369-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060845.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOVA2	NM_002516.4	c.970_972del	p.Ala324del	inframe_deletion	4/4	ENST00000263257.6
NOVA2	XM_006723230.4	c.643_645del	p.Ala215del	inframe_deletion	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOVA2	ENST00000263257.6	c.970_972del	p.Ala324del	inframe_deletion	4/4	1	NM_002516.4	P1
NOVA2	ENST00000676183.1	c.1162_1164del	p.Ala388del	inframe_deletion	4/4

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 149508 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000298

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000290 AC: 360 AN: 1242738 Hom.: 0 AF XY: 0.000292 AC XY: 179 AN XY: 612444

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.000758

Gnomad4 ASJ exome AF: 0.000563

Gnomad4 EAS exome AF: 0.000341

Gnomad4 SAS exome AF: 0.000890

Gnomad4 FIN exome AF: 0.000635

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.000427

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149508 Hom.: 0 Cov.: 32 AF XY: 0.0000274 AC XY: 2 AN XY: 72904

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000298

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NOVA2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs771592016; hg19: chr19-46443627;