Variant 10-84222111-C-T 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_001017924.5(LRIT2):c.1462G>A(p.Gly488Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,609,078 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 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

LRIT2
NM_001017924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

LRIT2 (HGNC:23443): (leucine rich repeat, Ig-like and transmembrane domains 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRIT2 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=0.024231642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIT2	NM_001017924.5 linkuse as main transcript	c.1462G>A	p.Gly488Ser	missense_variant	3/3	ENST00000372113.7
LRIT2	NM_001284223.1 linkuse as main transcript	c.1492G>A	p.Gly498Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIT2	ENST00000372113.7 linkuse as main transcript	c.1462G>A	p.Gly488Ser	missense_variant	3/3	1	NM_001017924.5	P2	A6NDA9-1
LRIT2	ENST00000538192.5 linkuse as main transcript	c.1492G>A	p.Gly498Ser	missense_variant	4/4	1		A2	A6NDA9-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000658

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000129

AC:

AN:

248018

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000235

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000244

AC:

355

AN:

1456728

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

174

AN XY:

723720

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000270

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000416

Gnomad4 NFE exome

AF:

0.000283

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000171

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000658

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

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

May 23, 2023

The c.1462G>A (p.G488S) alteration is located in exon 3 (coding exon 3) of the LRIT2 gene. This alteration results from a G to A substitution at nucleotide position 1462, causing the glycine (G) at amino acid position 488 to be replaced by a serine (S). 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

-0.50

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.58

N;N

REVEL

Benign

0.011

Sift

Benign

0.12

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.085

.;B

Vest4

0.051

MVP

0.28

MPC

0.0057

ClinPred

0.068

GERP RS

2.8

Varity_R

0.038

gMVP

0.20

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