Variant 4-25018010-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000382114.9(LGI2):c.634G>C(p.Asp212His) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LGI2
ENST00000382114.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3045287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI2	NM_018176.4 linkuse as main transcript	c.634G>C	p.Asp212His	missense_variant	6/8	ENST00000382114.9	NP_060646.2	Q8N0V4
LGI2	XM_011513850.3 linkuse as main transcript	c.634G>C	p.Asp212His	missense_variant	6/8		XP_011512152.1
LGI2	XM_017008356.2 linkuse as main transcript	c.634G>C	p.Asp212His	missense_variant	6/8		XP_016863845.1
LOC102723675	XR_007058082.1 linkuse as main transcript	n.1049-6720C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGI2	ENST00000382114.9 linkuse as main transcript	c.634G>C	p.Asp212His	missense_variant	6/8	1	NM_018176.4	ENSP00000371548.4		Q8N0V4
LGI2	ENST00000512108.1 linkuse as main transcript	c.604G>C	p.Asp202His	missense_variant	6/7	2		ENSP00000426254.1		H0YA65

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248828

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459252

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

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

Dec 06, 2022

The c.634G>C (p.D212H) alteration is located in exon 6 (coding exon 6) of the LGI2 gene. This alteration results from a G to C substitution at nucleotide position 634, causing the aspartic acid (D) at amino acid position 212 to be replaced by a histidine (H). 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

0.21

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

M_CAP

Benign

0.012

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.77

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.15

Sift

Benign

0.18

Sift4G

Benign

0.25

Polyphen

0.021

Vest4

0.42

MutPred

0.37

Loss of glycosylation at T217 (P = 0.0455);

MVP

0.86

MPC

0.57

ClinPred

0.28

GERP RS

5.7

Varity_R

0.41

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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