6-41336177-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004828.4(NCR2):c.143T>C(p.Leu48Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCR2 NM_004828.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.872

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053577214).
• BP6: Variant 6-41336177-T-C is Benign according to our data. Variant chr6-41336177-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2296888.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR2	NM_004828.4	c.143T>C	p.Leu48Pro	missense_variant	2/5	ENST00000373089.10
NCR2	NM_001199509.2	c.143T>C	p.Leu48Pro	missense_variant	2/6
NCR2	NM_001199510.2	c.143T>C	p.Leu48Pro	missense_variant	2/6
NCR2	XM_017011500.2	c.167T>C	p.Leu56Pro	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR2	ENST00000373089.10	c.143T>C	p.Leu48Pro	missense_variant	2/5	1	NM_004828.4	P2
NCR2	ENST00000373086.3	c.143T>C	p.Leu48Pro	missense_variant	2/6	1		A2
NCR2	ENST00000373083.8	c.143T>C	p.Leu48Pro	missense_variant	2/6	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.17
Dann	Benign	0.31
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00056	N
LIST_S2	Benign	0.23	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.74	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	4.0	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.067
MutPred		0.40		Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);
MVP		0.19
MPC		0.18
ClinPred		0.054	T
GERP RS		-0.84
Varity_R		0.19
gMVP		0.49

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: chr6-41303915;