Variant chr11-57476457-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000335099.8(RTN4RL2):c.809G>A(p.Arg270Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000707 in 1,556,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R270L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

RTN4RL2
ENST00000335099.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

RTN4RL2 (HGNC:23053): (reticulon 4 receptor like 2) Enables signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; corpus callosum development; and negative regulation of neuron projection development. Located in cell surface. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RTN4RL2 links:

ENSG00000255301 (HGNC:):

ENSG00000255301 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33062512).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN4RL2	NM_178570.3 linkuse as main transcript	c.809G>A	p.Arg270Gln	missense_variant	3/3	ENST00000335099.8	NP_848665.1	Q86UN3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN4RL2	ENST00000335099.8 linkuse as main transcript	c.809G>A	p.Arg270Gln	missense_variant	3/3	1	NM_178570.3	ENSP00000335397.3		Q86UN3-1
ENSG00000255301	ENST00000528885.1 linkuse as main transcript	n.*36C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000619

AC:

AN:

161450

Hom.:

AF XY:

0.00

AC XY:

AN XY:

91584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000138

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000569

AC:

AN:

1404986

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697410

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000518

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000457

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.809G>A (p.R270Q) alteration is located in exon 3 (coding exon 3) of the RTN4RL2 gene. This alteration results from a G to A substitution at nucleotide position 809, causing the arginine (R) at amino acid position 270 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Benign

0.15

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.13

Sift

Benign

0.089

Sift4G

Benign

0.13

Polyphen

0.94

Vest4

0.23

MutPred

0.47

Loss of MoRF binding (P = 0.0274);

MVP

0.40

MPC

1.6

ClinPred

0.91

GERP RS

4.3

Varity_R

0.46

gMVP

0.87

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