22-37570731-C-A

Variant names:

• chr22-37570731-C-A
• rs1451531094
• NM_006498.3:c.94G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006498.3(LGALS2):​c.94G>T​(p.Val32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LGALS2 NM_006498.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.14
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093969196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006498.3. 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
	LGALS2	NM_006498.3	MANE Select	c.94G>T	p.Val32Leu	missense	Exon 3 of 4	NP_006489.1	P05162

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS2	ENST00000215886.6	TSL:1 MANE Select	c.94G>T	p.Val32Leu	missense	Exon 3 of 4	ENSP00000215886.4	P05162

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.54
DANN	Benign	0.82
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.014
Sift	Benign	0.18	T
Sift4G	Benign	0.37	T
Polyphen		0.0040	B
Vest4		0.25
MutPred		0.49		Loss of sheet (P = 0.0817)
MVP		0.067
MPC		0.13
ClinPred		0.045	T
GERP RS		-6.4
Varity_R		0.36
gMVP		0.35
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1451531094; hg19: chr22-37966738;