2-99245284-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_175735.4(LYG2):​c.359G>A​(p.Gly120Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,454,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYG2 NM_175735.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.91

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>A	p.Gly120Glu	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>A	p.Gly120Glu	missense	Exon 5 of 7	ENSP00000327533.2	Q86SG7-1
	LYG2	ENST00000409679.5	TSL:1	c.359G>A	p.Gly120Glu	missense	Exon 4 of 5	ENSP00000386381.1	C9J4J0
	LYG2	ENST00000423800.5	TSL:1	c.359G>A	p.Gly120Glu	missense	Exon 3 of 6	ENSP00000390357.1	Q86SG7-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245526 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 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: 0.0000508 AC: 2 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: 0.00 AC: 0 AN: 1108246

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

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

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	Benign	0.28
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.2
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.78		Gain of solvent accessibility (P = 0.0145)
MVP		0.53
MPC		0.91
ClinPred		0.96	D
GERP RS		4.8
Varity_R		0.54
gMVP		0.75
Mutation Taster		=65/35	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: rs750993790; hg19: chr2-99861747;