11-57467614-G-T

Variant names:

• chr11-57467614-G-T
• NM_178570.3:c.37G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178570.3(RTN4RL2):​c.37G>T​(p.Ala13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RTN4RL2 NM_178570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13770732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN4RL2	NM_178570.3	c.37G>T	p.Ala13Ser	missense_variant	Exon 2 of 3	ENST00000335099.8	NP_848665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN4RL2	ENST00000335099.8	c.37G>T	p.Ala13Ser	missense_variant	Exon 2 of 3	1	NM_178570.3	ENSP00000335397.3
RTN4RL2	ENST00000395120.2	c.37G>T	p.Ala13Ser	missense_variant	Exon 2 of 3	1		ENSP00000378552.2
RTN4RL2	ENST00000533205.5	c.37G>T	p.Ala13Ser	missense_variant	Exon 2 of 3	3		ENSP00000435606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452254 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 721586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37G>T (p.A13S) alteration is located in exon 2 (coding exon 2) of the RTN4RL2 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a serine (S). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.30	B;.;.
Vest4		0.42
MutPred		0.32		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);
MVP		0.57
MPC		1.6
ClinPred		0.46	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57235087;