chr3-46529920-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024512.5(LRRC2):c.758C>T(p.Pro253Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,912 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: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
LRRC2
NM_024512.5 missense
NM_024512.5 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 9.12
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 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, 0.895
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC2 | NM_024512.5 | c.758C>T | p.Pro253Leu | missense_variant | 6/9 | ENST00000395905.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC2 | ENST00000395905.8 | c.758C>T | p.Pro253Leu | missense_variant | 6/9 | 1 | NM_024512.5 | P1 | |
LRRC2 | ENST00000296144.3 | c.758C>T | p.Pro253Leu | missense_variant | 6/9 | 1 | P1 | ||
LRRC2 | ENST00000682605.1 | c.758C>T | p.Pro253Leu | missense_variant | 6/9 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251198Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135772
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461766Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727174
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
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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 26, 2022 | The c.758C>T (p.P253L) alteration is located in exon 6 (coding exon 5) of the LRRC2 gene. This alteration results from a C to T substitution at nucleotide position 758, causing the proline (P) at amino acid position 253 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0448);Loss of disorder (P = 0.0448);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
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