2-99246722-T-A

Position:

• chr2-99246722-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_175735.4(LYG2):​c.142A>T​(p.Thr48Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYG2 NM_175735.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.710

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYG2	NM_175735.4	c.142A>T	p.Thr48Ser	missense_variant	4/7	ENST00000333017.7	NP_783862.2
LYG2	XM_017003751.3	c.142A>T	p.Thr48Ser	missense_variant	4/7		XP_016859240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYG2	ENST00000333017.7	c.142A>T	p.Thr48Ser	missense_variant	4/7	5	NM_175735.4	ENSP00000327533	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.142A>T (p.T48S) alteration is located in exon 3 (coding exon 2) of the LYG2 gene. This alteration results from a A to T substitution at nucleotide position 142, causing the threonine (T) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.;.;.;T
Eigen	Benign	0.093
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.52	.;T;.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M;M;M;M;.;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D;D;D;.;D;D
REVEL	Benign	0.22
Sift	Benign	0.039	D;D;D;.;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D;.
Polyphen		0.98	D;D;.;.;P;.
Vest4		0.42
MutPred		0.85		Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);Gain of disorder (P = 0.0605);
MVP		0.30
MPC		0.40
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.17
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1169834531; hg19: chr2-99863185;