chr3-46539143-G-A

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

4
9
6

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]

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
LRRC2NM_024512.5 linkuse as main transcriptc.392C>T p.Thr131Ile missense_variant 4/9 ENST00000395905.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRC2ENST00000395905.8 linkuse as main transcriptc.392C>T p.Thr131Ile missense_variant 4/91 NM_024512.5 P1
LRRC2ENST00000296144.3 linkuse as main transcriptc.392C>T p.Thr131Ile missense_variant 4/91 P1
LRRC2ENST00000682605.1 linkuse as main transcriptc.392C>T p.Thr131Ile missense_variant 4/9 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461528
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
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.:
32

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 submitterclinical testingAmbry GeneticsMay 18, 2023The 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
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.012
T
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.9
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.63
T
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
D
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.

Other links and lift over

hg19: chr3-46580633; API