Variant 10-84222065-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.1508G>A(p.Arg503His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,610,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.00044 ( 0 hom. )

Consequence

LRIT2
NM_001017924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420

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=0.024829954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIT2	NM_001017924.5 linkuse as main transcript	c.1508G>A	p.Arg503His	missense_variant	3/3	ENST00000372113.7
LRIT2	NM_001284223.1 linkuse as main transcript	c.1538G>A	p.Arg513His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIT2	ENST00000372113.7 linkuse as main transcript	c.1508G>A	p.Arg503His	missense_variant	3/3	1	NM_001017924.5	P2	A6NDA9-1
LRIT2	ENST00000538192.5 linkuse as main transcript	c.1538G>A	p.Arg513His	missense_variant	4/4	1		A2	A6NDA9-2

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000388

AC:

AN:

247208

Hom.:

AF XY:

0.000374

AC XY:

AN XY:

133770

show subpopulations

Gnomad AFR exome

AF:

0.000254

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.000207

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.000607

Gnomad NFE exome

AF:

0.000510

Gnomad OTH exome

AF:

0.000833

GnomAD4 exome

AF:

0.000441

AC:

643

AN:

1458242

Hom.:

Cov.:

AF XY:

0.000439

AC XY:

318

AN XY:

724956

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.000358

Gnomad4 NFE exome

AF:

0.000493

Gnomad4 OTH exome

AF:

0.000432

GnomAD4 genome

AF:

0.000335

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.000382

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000712

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

Jul 27, 2021

The c.1508G>A (p.R503H) 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 1508, causing the arginine (R) at amino acid position 503 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

0.069

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.71

Cadd

Benign

0.34

Dann

Benign

0.96

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.023

Sift

Benign

0.19

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.032

.;B

Vest4

0.049

MVP

0.12

MPC

0.0049

ClinPred

0.0083

GERP RS

-0.051

Varity_R

0.038

gMVP

0.14

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