Genetic Variant LGALS2:p.Val119Ile (chr22-37570307-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006498.3(LGALS2):c.355G>A(p.Val119Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,530 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.040 ( 397 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 503 hom. )

Consequence

LGALS2
NM_006498.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900

Publications

9 publications found

Variant links:

Genes affected

LGALS2 (HGNC:6562): (galectin 2) The protein encoded by this gene is a soluble beta-galactoside binding lectin. The encoded protein is found as a homodimer and can bind to lymphotoxin-alpha. A single nucleotide polymorphism in an intron of this gene can alter the transcriptional level of the protein, with a resultant increased risk of myocardial infarction. [provided by RefSeq, Jul 2008]

LGALS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016162395).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS2	NM_006498.3 link	c.355G>A	p.Val119Ile	missense_variant	Exon 4 of 4	ENST00000215886.6	NP_006489.1	P05162

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS2	ENST00000215886.6 link	c.355G>A	p.Val119Ile	missense_variant	Exon 4 of 4	1	NM_006498.3	ENSP00000215886.4		P05162

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6139

AN:

152166

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0426

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.0254

GnomAD2 exomes

AF:

0.0139

AC:

3490

AN:

251376

AF XY:

0.0115

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.00752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.000774

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00709

AC:

10364

AN:

1461246

Hom.:

503

Cov.:

AF XY:

0.00679

AC XY:

4936

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.140

AC:

4672

AN:

33458

American (AMR)

AF:

0.00808

AC:

361

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.0711

AC:

2820

AN:

39678

South Asian (SAS)

AF:

0.00950

AC:

819

AN:

86236

European-Finnish (FIN)

AF:

0.000917

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000584

AC:

649

AN:

1111524

Other (OTH)

AF:

0.0153

AC:

921

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

523

1046

1569

2092

2615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.0404

AC:

6149

AN:

152284

Hom.:

397

Cov.:

AF XY:

0.0391

AC XY:

2910

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.133

AC:

5533

AN:

41524

American (AMR)

AF:

0.0138

AC:

211

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0425

AC:

221

AN:

5194

South Asian (SAS)

AF:

0.00870

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000955

AC:

AN:

68028

Other (OTH)

AF:

0.0251

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

276

552

828

1104

1380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0214

Hom.:

1179

Bravo

AF:

0.0448

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.126

AC:

553

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0161

AC:

1954

Asia WGS

AF:

0.0470

AC:

162

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.018

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PhyloP100

0.0090

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.31

REVEL

Benign

0.011

Sift

Benign

0.47

Sift4G

Benign

0.49

Polyphen

0.15

Vest4

0.023

MPC

0.17

ClinPred

0.0014

GERP RS

-0.012

Varity_R

0.074

gMVP

0.19

Mutation Taster

=96/4

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over