Variant 6-41342064-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.559C>T(p.Pro187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NCR2
NM_004828.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

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=0.03642246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR2	NM_004828.4 linkuse as main transcript	c.559C>T	p.Pro187Ser	missense_variant	4/5	ENST00000373089.10	NP_004819.2	O95944-1
NCR2	NM_001199509.2 linkuse as main transcript	c.595C>T	p.Pro199Ser	missense_variant	4/6		NP_001186438.1	O95944-2
NCR2	NM_001199510.2 linkuse as main transcript	c.559C>T	p.Pro187Ser	missense_variant	4/6		NP_001186439.1	O95944-3
NCR2	XM_017011500.2 linkuse as main transcript	c.583C>T	p.Pro195Ser	missense_variant	4/5		XP_016866989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NCR2	ENST00000373089.10 linkuse as main transcript	c.559C>T	p.Pro187Ser	missense_variant	4/5	1	NM_004828.4	ENSP00000362181.5	O95944-1
NCR2	ENST00000373086.3 linkuse as main transcript	c.595C>T	p.Pro199Ser	missense_variant	4/6	1		ENSP00000362178.3	O95944-2
NCR2	ENST00000373083.8 linkuse as main transcript	c.559C>T	p.Pro187Ser	missense_variant	4/6	1		ENSP00000362175.4	O95944-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251280

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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

Oct 06, 2021

The c.559C>T (p.P187S) alteration is located in exon 4 (coding exon 4) of the NCR2 gene. This alteration results from a C to T substitution at nucleotide position 559, causing the proline (P) at amino acid position 187 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

0.091

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.8

DANN

Benign

0.20

DEOGEN2

Benign

0.051

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.97

L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.030

N;N;N

REVEL

Benign

0.0030

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.11

B;B;B

Vest4

0.21

MutPred

0.28

Gain of phosphorylation at P187 (P = 0.0537);Gain of phosphorylation at P187 (P = 0.0537);.;

MVP

0.15

MPC

0.13

ClinPred

0.015

GERP RS

0.85

Varity_R

0.022

gMVP

0.10

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