dbSNP rs746129231: RTN4RL2:p.Arg278Ser (chr11-57476480-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178570.3(RTN4RL2):c.832C>A(p.Arg278Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,238 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

RTN4RL2
NM_178570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.358

Publications

0 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:

ENSG00000255301 (HGNC:):

ENSG00000255301 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12356961).

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.832C>A	p.Arg278Ser	missense	Exon 3 of 3	NP_848665.1	Q86UN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4RL2	ENST00000335099.8	TSL:1 MANE Select	c.832C>A	p.Arg278Ser	missense	Exon 3 of 3	ENSP00000335397.3	Q86UN3-1
	ENSG00000255301	ENST00000528885.1	TSL:2	n.*13G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

117734

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1360238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28190

American (AMR)

AF:

0.00

AC:

AN:

32168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23078

East Asian (EAS)

AF:

0.00

AC:

AN:

33154

South Asian (SAS)

AF:

0.00

AC:

AN:

75520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071626

Other (OTH)

AF:

0.0000177

AC:

AN:

56486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000185

AC:

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

0.21

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.39

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.57

PhyloP100

-0.36

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.075

Sift

Benign

0.39

Sift4G

Benign

0.30

Polyphen

0.031

Vest4

0.19

MutPred

0.37

Loss of MoRF binding (P = 0.0359)

MVP

0.14

MPC

1.3

ClinPred

0.70

GERP RS

3.4

Varity_R

0.64

gMVP

0.73

Mutation Taster

=91/9

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over