chr9-128150254-A-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005564.5(LCN2):c.155A>G(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,834 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
LCN2
NM_005564.5 missense
NM_005564.5 missense
Scores
6
5
8
Clinical Significance
Conservation
PhyloP100: 1.75
Publications
1 publications found
Genes affected
LCN2 (HGNC:6526): (lipocalin 2) This gene encodes a protein that belongs to the lipocalin family. Members of this family transport small hydrophobic molecules such as lipids, steroid hormones and retinoids. The protein encoded by this gene is a neutrophil gelatinase-associated lipocalin and plays a role in innate immunity by limiting bacterial growth as a result of sequestering iron-containing siderophores. The presence of this protein in blood and urine is an early biomarker of acute kidney injury. This protein is thought to be be involved in multiple cellular processes, including maintenance of skin homeostasis, and suppression of invasiveness and metastasis. Mice lacking this gene are more susceptible to bacterial infection than wild type mice. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.948
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152138
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251236 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251236
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727138 show subpopulations
GnomAD4 exome
AF:
AC:
15
AN:
1461696
Hom.:
Cov.:
31
AF XY:
AC XY:
7
AN XY:
727138
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26116
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
14
AN:
1111902
Other (OTH)
AF:
AC:
1
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74314 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152138
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74314
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41426
American (AMR)
AF:
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68022
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Oct 20, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.155A>G (p.Y52C) alteration is located in exon 2 (coding exon 2) of the LCN2 gene. This alteration results from a A to G substitution at nucleotide position 155, causing the tyrosine (Y) at amino acid position 52 to be replaced by a cysteine (C). 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
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of methylation at K50 (P = 0.1126);Gain of methylation at K50 (P = 0.1126);Gain of methylation at K50 (P = 0.1126);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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