chr3-46539186-A-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_024512.5(LRRC2):c.349T>A(p.Leu117Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,613,770 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 4 hom. )
Consequence
LRRC2
NM_024512.5 missense
NM_024512.5 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: -0.138
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007152617).
BP6
Variant 3-46539186-A-T is Benign according to our data. Variant chr3-46539186-A-T is described in ClinVar as [Benign]. Clinvar id is 712053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC2 | NM_024512.5 | c.349T>A | p.Leu117Met | missense_variant | 4/9 | ENST00000395905.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC2 | ENST00000395905.8 | c.349T>A | p.Leu117Met | missense_variant | 4/9 | 1 | NM_024512.5 | P1 | |
LRRC2 | ENST00000296144.3 | c.349T>A | p.Leu117Met | missense_variant | 4/9 | 1 | P1 | ||
LRRC2 | ENST00000682605.1 | c.349T>A | p.Leu117Met | missense_variant | 4/9 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00375 AC: 571AN: 152200Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000984 AC: 247AN: 250996Hom.: 3 AF XY: 0.000715 AC XY: 97AN XY: 135678
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GnomAD4 exome AF: 0.000458 AC: 669AN: 1461452Hom.: 4 Cov.: 31 AF XY: 0.000426 AC XY: 310AN XY: 727026
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GnomAD4 genome AF: 0.00375 AC: 571AN: 152318Hom.: 4 Cov.: 32 AF XY: 0.00371 AC XY: 276AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at