22-37570307-C-T

Position:

• chr22-37570307-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.040 (397 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (503 hom.)
• Consequence: LGALS2 NM_006498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LGALS2	NM_006498.3	c.355G>A	p.Val119Ile	missense_variant	4/4	ENST00000215886.6	NP_006489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS2	ENST00000215886.6	c.355G>A	p.Val119Ile	missense_variant	4/4	1	NM_006498.3	ENSP00000215886.4

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6139 AN: 152166 Hom.: 398 Cov.: 33

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

GnomAD3 exomes AF: 0.0139 AC: 3490 AN: 251376 Hom.: 163 AF XY: 0.0115 AC XY: 1557 AN XY: 135856

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 SAS exome AF: 0.00964

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.: 31 AF XY: 0.00679 AC XY: 4936 AN XY: 726794

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.00808

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0711

Gnomad4 SAS exome AF: 0.00950

Gnomad4 FIN exome AF: 0.000917

Gnomad4 NFE exome AF: 0.000584

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0404 AC: 6149 AN: 152284 Hom.: 397 Cov.: 33 AF XY: 0.0391 AC XY: 2910 AN XY: 74464

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0164 Hom.: 970

Bravo AF: 0.0448

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.126 AC: 553

ESP6500EA AF: 0.000349 AC: 3

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	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.76
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.011
Sift	Benign	0.47	T
Sift4G	Benign	0.49	T
Polyphen		0.15	B
Vest4		0.023
MPC		0.17
ClinPred		0.0014	T
GERP RS		-0.012
Varity_R		0.074
gMVP		0.19

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

Other links and lift over

dbSNP: rs2235339; hg19: chr22-37966314; COSMIC: COSV50755876; COSMIC: COSV50755876;