Variant 15-76931855-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002902.3(RCN2):c.14C>T(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,268,710 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RCN2
NM_002902.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0790

Variant links:

Genes affected

RCN2 (HGNC:9935): (reticulocalbin 2) The protein encoded by this gene is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. This gene maps to the same region as type 4 Bardet-Biedl syndrome, suggesting a possible causative role for this gene in the disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

RCN2 links:

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ACMG classification

Classification made for transcript

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=0.2206645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCN2	NM_002902.3 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	1/7	ENST00000394885.8
RCN2	NM_001271837.2 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCN2	ENST00000394885.8 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	1/7	1	NM_002902.3	P1	Q14257-1
RCN2	ENST00000320963.9 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	1/8	5			Q14257-2
RCN2	ENST00000394883.3 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	1/5	5
RCN2	ENST00000557805.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1117164

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

540470

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000276

Gnomad4 OTH exome

AF:

0.0000456

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000189

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.14C>T (p.P5L) alteration is located in exon 1 (coding exon 1) of the RCN2 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.67

T;T;T

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

0.96

D;D;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.0

B;.;B

Vest4

0.25

MutPred

0.22

Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);

MVP

0.60

MPC

0.41

ClinPred

0.54

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.041

gMVP

0.37

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