20-45890585-C-CT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_080749.4(NEURL2):c.406_407insA(p.Ser136LysfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,612,316 control chromosomes in the GnomAD database, including 41 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (40 hom.)
• Consequence: NEURL2 NM_080749.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.00

Genes affected

NEURL2 (HGNC:16156): (neuralized E3 ubiquitin protein ligase 2) This gene encodes a protein that is involved in the regulation of myofibril organization. This protein is likely the adaptor component of the E3 ubiquitin ligase complex in striated muscle, and it regulates the ubiquitin-mediated degradation of beta-catenin during myogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2013]

CTSA (HGNC:9251): (cathepsin A) This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis. [provided by RefSeq, Nov 2015]

SPATA25 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-45890585-C-CT is Benign according to our data. Variant chr20-45890585-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1206356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEURL2	NM_080749.4	c.406_407insA	p.Ser136LysfsTer15	frameshift_variant	1/2	ENST00000372518.5
NEURL2	NM_001278535.2	c.406_407insA	p.Ser136LysfsTer15	frameshift_variant	1/2
SPATA25	XM_024451826.2	c.-2158_-2157insA		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEURL2	ENST00000372518.5	c.406_407insA	p.Ser136LysfsTer15	frameshift_variant	1/2	1	NM_080749.4	P1

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00772

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00417 AC: 1020 AN: 244612 Hom.: 5 AF XY: 0.00432 AC XY: 577 AN XY: 133568

Gnomad AFR exome AF: 0.000941

Gnomad AMR exome AF: 0.000844

Gnomad ASJ exome AF: 0.00762

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.00239

Gnomad NFE exome AF: 0.00715

Gnomad OTH exome AF: 0.00488

GnomAD4 exome AF: 0.00655 AC: 9556 AN: 1459970 Hom.: 40 Cov.: 38 AF XY: 0.00640 AC XY: 4647 AN XY: 726182

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00906

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.00276

Gnomad4 NFE exome AF: 0.00779

Gnomad4 OTH exome AF: 0.00559

GnomAD4 genome AF: 0.00466 AC: 710 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.00421 AC XY: 314 AN XY: 74506

Gnomad4 AFR AF: 0.00139

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.00772

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00636 Hom.: 1

Bravo AF: 0.00465

EpiCase AF: 0.00747

EpiControl AF: 0.00694

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	NEURL2: BS2 -

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: rs201802475; hg19: chr20-44519224;