Genetic Variant RTN4RL2:p.Arg7Cys (chr11-57460884-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178570.3(RTN4RL2):c.19C>T(p.Arg7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,406,832 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

RTN4RL2
NM_178570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015383929).

BS2

High AC in GnomAd4 at 117 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4RL2	NM_178570.3	MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	NP_848665.1	Q86UN3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTN4RL2	ENST00000335099.8	TSL:1 MANE Select	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000335397.3	Q86UN3-1
RTN4RL2	ENST00000395120.2	TSL:1	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000378552.2	Q86UN3-2
RTN4RL2	ENST00000533205.5	TSL:3	c.19C>T	p.Arg7Cys	missense	Exon 1 of 3	ENSP00000435606.1	G3V1D7

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

114

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000106

AC:

AN:

84972

AF XY:

0.0000837

show subpopulations

Gnomad AFR exome

AF:

0.00242

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000638

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

142

AN:

1254654

Hom.:

Cov.:

AF XY:

0.0000862

AC XY:

AN XY:

614924

show subpopulations

African (AFR)

AF:

0.00381

AC:

AN:

25724

American (AMR)

AF:

0.000139

AC:

AN:

21512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21326

East Asian (EAS)

AF:

0.00

AC:

AN:

27536

South Asian (SAS)

AF:

0.0000485

AC:

AN:

61796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44290

Middle Eastern (MID)

AF:

0.000544

AC:

AN:

3678

European-Non Finnish (NFE)

AF:

0.0000130

AC:

AN:

998622

Other (OTH)

AF:

0.000458

AC:

AN:

50170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000769

AC:

117

AN:

152178

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41548

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67954

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000941

ExAC

AF:

0.000101

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.6

PhyloP100

1.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Uncertain

0.0010

Sift4G

Benign

0.18

Polyphen

0.66

Vest4

0.13

MVP

0.41

MPC

2.2

ClinPred

0.063

GERP RS

3.0

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.28

gMVP

0.70

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over