NM_014813.3:c.463A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014813.3(LRIG2):c.463A>T(p.Ile155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,611,062 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

LRIG2
NM_014813.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.161

Publications

2 publications found

Variant links:

Genes affected

LRIG2 (HGNC:20889): (leucine rich repeats and immunoglobulin like domains 2) This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

LRIG2 Gene-Disease associations (from GenCC):

urofacial syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Ochoa syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LRIG2 links:

ENSG00000303525 (HGNC:):

ENSG00000303525 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005778134).

BP6

Variant 1-113093512-A-T is Benign according to our data. Variant chr1-113093512-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 730524.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00259 (393/151836) while in subpopulation AFR AF = 0.00895 (371/41432). AF 95% confidence interval is 0.0082. There are 2 homozygotes in GnomAd4. There are 177 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014813.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG2	NM_014813.3	MANE Select	c.463A>T	p.Ile155Leu	missense	Exon 4 of 18	NP_055628.1	O94898
	LRIG2	NM_001312686.2		c.154A>T	p.Ile52Leu	missense	Exon 5 of 19	NP_001299615.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRIG2	ENST00000361127.6	TSL:1 MANE Select	c.463A>T	p.Ile155Leu	missense	Exon 4 of 18	ENSP00000355396.4	O94898
LRIG2	ENST00000922864.1		c.463A>T	p.Ile155Leu	missense	Exon 4 of 19	ENSP00000592923.1
LRIG2	ENST00000890456.1		c.397A>T	p.Ile133Leu	missense	Exon 3 of 17	ENSP00000560515.1

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

381

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000513

AC:

129

AN:

251338

AF XY:

0.000331

show subpopulations

Gnomad AFR exome

AF:

0.00710

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000230

AC:

335

AN:

1459226

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

726058

show subpopulations

African (AFR)

AF:

0.00787

AC:

263

AN:

33416

American (AMR)

AF:

0.000515

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1109812

Other (OTH)

AF:

0.000514

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00259

AC:

393

AN:

151836

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.00895

AC:

371

AN:

41432

American (AMR)

AF:

0.000721

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10494

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67926

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.00263

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000692

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

LRIG2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.4

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.98

PhyloP100

0.16

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

REVEL

Benign

0.070

Sift

Benign

0.35

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.13

MutPred

0.22

Loss of methylation at K160 (P = 0.061)

MVP

0.47

MPC

0.16

ClinPred

0.0071

GERP RS

-1.6

Varity_R

0.054

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over