Variant 4-25012435-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000382114.9(LGI2):c.720C>A(p.Asn240Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 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: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LGI2
ENST00000382114.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0690

Variant links:

Genes affected

LGI2 (HGNC:18710): (leucine rich repeat LGI family member 2) Predicted to be involved in inhibitory synapse assembly. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LGI2 links:

LOC102723675 (HGNC:):

LOC102723675 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI2	NM_018176.4 linkuse as main transcript	c.720C>A	p.Asn240Lys	missense_variant	7/8	ENST00000382114.9	NP_060646.2	Q8N0V4
LGI2	XM_011513850.3 linkuse as main transcript	c.720C>A	p.Asn240Lys	missense_variant	7/8		XP_011512152.1
LGI2	XM_017008356.2 linkuse as main transcript	c.720C>A	p.Asn240Lys	missense_variant	7/8		XP_016863845.1
LOC102723675	XR_007058082.1 linkuse as main transcript	n.1049-12295G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI2	ENST00000382114.9 linkuse as main transcript	c.720C>A	p.Asn240Lys	missense_variant	7/8	1	NM_018176.4	ENSP00000371548.4		Q8N0V4
LGI2	ENST00000512108.1 linkuse as main transcript	c.625+5554C>A		intron_variant		2		ENSP00000426254.1		H0YA65

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 07, 2023

The c.720C>A (p.N240K) alteration is located in exon 7 (coding exon 7) of the LGI2 gene. This alteration results from a C to A substitution at nucleotide position 720, causing the asparagine (N) at amino acid position 240 to be replaced by a lysine (K). 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

0.17

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Benign

8.7

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.84

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.52

Sift

Benign

0.046

Sift4G

Benign

0.16

Polyphen

0.79

Vest4

0.87

MutPred

0.58

Gain of ubiquitination at N240 (P = 0.0131);

MVP

0.83

MPC

0.89

ClinPred

0.99

GERP RS

-2.1

Varity_R

0.43

gMVP

0.53

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over