Variant 20-45890585-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.00

Variant links:

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]

NEURL2 links:

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]

CTSA links:

SPATA25 (HGNC:):

SPATA25 links:

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ACMG classification

Classification made for transcript

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 GnomAdExome4 at 40 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEURL2	ENST00000372518.5 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00432

AC XY:

577

AN XY:

133568

show subpopulations

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.:

Cov.:

AF XY:

0.00640

AC XY:

4647

AN XY:

726182

show subpopulations

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.:

Cov.:

AF XY:

0.00421

AC XY:

314

AN XY:

74506

show subpopulations

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.:

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

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over