rs750993790

Variant names:

• chr2-99245284-C-A
• rs750993790
• NM_175735.4:c.359G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-99245284-C-A
• chr2-99245284-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_175735.4(LYG2):​c.359G>T​(p.Gly120Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G120E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LYG2 NM_175735.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

Genes affected

LYG2 (HGNC:29615): (lysozyme g2) The protein encoded by this gene contains a SLT domain, a protein domain present in bacterial lytic transglycosylase (SLT) and in eukaryotic lysozymes (GEWL). SLT domain catalyzes the cleavage of the beta-1,4-glycosidic bond between N-acetylmuramic acid (MurNAc) and N-acetyglucosamine (GlcNAc). [provided by RefSeq, Jul 2008]

ENSG00000241962 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175735.4. 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
	LYG2	NM_175735.4	MANE Select	c.359G>T	p.Gly120Val	missense	Exon 5 of 7	NP_783862.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYG2	ENST00000333017.7	TSL:5 MANE Select	c.359G>T	p.Gly120Val	missense	Exon 5 of 7	ENSP00000327533.2	Q86SG7-1
	LYG2	ENST00000409679.5	TSL:1	c.359G>T	p.Gly120Val	missense	Exon 4 of 5	ENSP00000386381.1	C9J4J0
	LYG2	ENST00000423800.5	TSL:1	c.359G>T	p.Gly120Val	missense	Exon 3 of 6	ENSP00000390357.1	Q86SG7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454556 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723394

African (AFR) AF: 0.00 AC: 0 AN: 33234

American (AMR) AF: 0.00 AC: 0 AN: 43826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39342

South Asian (SAS) AF: 0.00 AC: 0 AN: 84828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108246

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.80		Loss of disorder (P = 0.0929)
MVP		0.55
MPC		0.90
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.58
gMVP		0.82
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.75		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.75		Position offset: 2

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

Other links and lift over

dbSNP: rs750993790; hg19: chr2-99861747;