20-45891004-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080749.4(NEURL2):c.-13C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,475,728 control chromosomes in the GnomAD database, including 219,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17795 hom., cov: 33)

Exomes 𝑓: 0.55 ( 202023 hom. )

Consequence

NEURL2
NM_080749.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 20-45891004-G-A is Benign according to our data. Variant chr20-45891004-G-A is described in ClinVar as [Benign]. Clinvar id is 338513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-45891004-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NEURL2	NM_080749.4 linkuse as main transcript	c.-13C>T	5_prime_UTR_variant	1/2	ENST00000372518.5
NEURL2	NM_001278535.2 linkuse as main transcript	c.-13C>T	5_prime_UTR_variant	1/2
SPATA25	XM_024451826.2 linkuse as main transcript	c.-2576C>T	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.-13C>T		5_prime_UTR_variant	1/2	1	NM_080749.4	P1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69075

AN:

151970

Hom.:

17785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.462

GnomAD3 exomes

AF:

0.506

AC:

46132

AN:

91100

Hom.:

12327

AF XY:

0.505

AC XY:

24311

AN XY:

48174

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.444

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

AF:

0.547

AC:

723529

AN:

1323640

Hom.:

202023

Cov.:

AF XY:

0.543

AC XY:

350018

AN XY:

644848

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.612

Gnomad4 ASJ exome

AF:

0.380

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.614

Gnomad4 NFE exome

AF:

0.573

Gnomad4 OTH exome

AF:

0.502

GnomAD4 genome

AF:

0.454

AC:

69092

AN:

152088

Hom.:

17795

Cov.:

AF XY:

0.457

AC XY:

33945

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.572

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.611

Gnomad4 NFE

AF:

0.568

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.535

Hom.:

23079

Bravo

AF:

0.442

Asia WGS

AF:

0.367

AC:

1278

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Combined deficiency of sialidase AND beta galactosidase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

Cadd

Benign

2.3

Dann

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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