Variant 3-46539143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024512.5(LRRC2):c.392C>T(p.Thr131Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRRC2
NM_024512.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.21

Variant links:

Genes affected

LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

LRRC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC2	NM_024512.5 linkuse as main transcript	c.392C>T	p.Thr131Ile	missense_variant	4/9	ENST00000395905.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC2	ENST00000395905.8 linkuse as main transcript	c.392C>T	p.Thr131Ile	missense_variant	4/9	1	NM_024512.5	P1
LRRC2	ENST00000296144.3 linkuse as main transcript	c.392C>T	p.Thr131Ile	missense_variant	4/9	1		P1
LRRC2	ENST00000682605.1 linkuse as main transcript	c.392C>T	p.Thr131Ile	missense_variant	4/9			P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727078

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 18, 2023

The c.392C>T (p.T131I) alteration is located in exon 4 (coding exon 3) of the LRRC2 gene. This alteration results from a C to T substitution at nucleotide position 392, causing the threonine (T) at amino acid position 131 to be replaced by an isoleucine (I). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;T

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.41

Sift

Benign

0.085

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.94

MutPred

0.78

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.47

MPC

0.95

ClinPred

1.0

GERP RS

5.0

Varity_R

0.38

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over