Variant 6-41341826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004828.4(NCR2):c.427C>T(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,612,630 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 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

NCR2
NM_004828.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.902

Variant links:

Genes affected

NCR2 (HGNC:6732): (natural cytotoxicity triggering receptor 2) Predicted to enable signaling receptor activity. Predicted to be involved in cellular defense response and signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

NCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066967726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCR2	NM_004828.4 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/5	ENST00000373089.10
NCR2	NM_001199509.2 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/6
NCR2	NM_001199510.2 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/6
NCR2	XM_017011500.2 linkuse as main transcript	c.451C>T	p.Arg151Cys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR2	ENST00000373089.10 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/5	1	NM_004828.4	P2	O95944-1
NCR2	ENST00000373086.3 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/6	1		A2	O95944-2
NCR2	ENST00000373083.8 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	3/6	1		A2	O95944-3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000162

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000167

AC:

AN:

250912

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000160

AC:

234

AN:

1460466

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000118

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

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

Apr 13, 2022

The c.427C>T (p.R143C) alteration is located in exon 3 (coding exon 3) of the NCR2 gene. This alteration results from a C to T substitution at nucleotide position 427, causing the arginine (R) at amino acid position 143 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.079

T;T;T

Sift4G

Benign

0.089

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.092

MVP

0.32

MPC

0.15

ClinPred

0.048

GERP RS

-0.070

Varity_R

0.059

gMVP

0.26

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