NM_006498.3:c.260C>T

Variant names:

• chr22-37570402-G-A
• rs73884090
• NM_006498.3:c.260C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006498.3(LGALS2):​c.260C>T​(p.Thr87Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,613,560 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (206 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (167 hom.)
• Consequence: LGALS2 NM_006498.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.19
• Publications: 6 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026144981).
• BP6: Variant 22-37570402-G-A is Benign according to our data. Variant chr22-37570402-G-A is described in ClinVar as Benign. ClinVar VariationId is 718695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

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.260C>T	p.Thr87Ile	missense	Exon 4 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.260C>T	p.Thr87Ile	missense	Exon 4 of 4	ENSP00000215886.4	P05162

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4157 AN: 152184 Hom.: 206 Cov.: 33

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00711 AC: 1787 AN: 251328 AF XY: 0.00536

Gnomad AFR exome AF: 0.0973

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00273 AC: 3986 AN: 1461258 Hom.: 167 Cov.: 32 AF XY: 0.00236 AC XY: 1718 AN XY: 726914

African (AFR) AF: 0.0963 AC: 3223 AN: 33456

American (AMR) AF: 0.00490 AC: 219 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00366 AC: 20 AN: 5466

European-Non Finnish (NFE) AF: 0.000112 AC: 125 AN: 1111818

Other (OTH) AF: 0.00633 AC: 382 AN: 60330

GnomAD4 genome AF: 0.0273 AC: 4163 AN: 152302 Hom.: 206 Cov.: 33 AF XY: 0.0264 AC XY: 1967 AN XY: 74476

African (AFR) AF: 0.0959 AC: 3986 AN: 41544

American (AMR) AF: 0.00732 AC: 112 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68038

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0106 Hom.: 160

Bravo AF: 0.0310

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0892 AC: 393

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00876 AC: 1064

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.064
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.034	D
Polyphen		0.97	D
Vest4		0.15
MVP		0.30
MPC		0.60
ClinPred		0.030	T
GERP RS		2.4
Varity_R		0.25
gMVP		0.30
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73884090; hg19: chr22-37966409;