Variant 5-135951265-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002302.3(LECT2):c.247A>G(p.Asn83Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

LECT2
NM_002302.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

LECT2 (HGNC:6550): (leukocyte cell derived chemotaxin 2) This gene encodes a secreted, 16 kDa protein that acts as a chemotactic factor to neutrophils and stimulates the growth of chondrocytes and osteoblasts. This protein has high sequence similarity to the chondromodulin repeat regions of the chicken myb-induced myeloid 1 protein. A polymorphism in this gene may be associated with rheumatoid arthritis. [provided by RefSeq, Jul 2008]

LECT2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04052931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LECT2	NM_002302.3 linkuse as main transcript	c.247A>G	p.Asn83Asp	missense_variant	3/4	ENST00000274507.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LECT2	ENST00000274507.6 linkuse as main transcript	c.247A>G	p.Asn83Asp	missense_variant	3/4	1	NM_002302.3	P1
	ENST00000467490.5 linkuse as main transcript	n.1416T>C		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

251480

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000330

AC:

483

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

219

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000405

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000328

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Dec 13, 2023

The c.247A>G (p.N83D) alteration is located in exon 3 (coding exon 3) of the LECT2 gene. This alteration results from a A to G substitution at nucleotide position 247, causing the asparagine (N) at amino acid position 83 to be replaced by an aspartic acid (D). 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

Benign

0.094

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.041

T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.93

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.95

N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.14

MVP

0.21

MPC

0.028

ClinPred

0.050

GERP RS

3.3

Varity_R

0.18

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over