Variant 2-99245408-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175735.4(LYG2):c.235C>T(p.Pro79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LYG2
NM_175735.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.185

Variant links:

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]

LYG2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066734135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYG2	NM_175735.4 linkuse as main transcript	c.235C>T	p.Pro79Ser	missense_variant	5/7	ENST00000333017.7	NP_783862.2
LYG2	XM_017003751.3 linkuse as main transcript	c.235C>T	p.Pro79Ser	missense_variant	5/7		XP_016859240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYG2	ENST00000333017.7 linkuse as main transcript	c.235C>T	p.Pro79Ser	missense_variant	5/7	5	NM_175735.4	ENSP00000327533	P1	Q86SG7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459732

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.235C>T (p.P79S) alteration is located in exon 4 (coding exon 3) of the LYG2 gene. This alteration results from a C to T substitution at nucleotide position 235, causing the proline (P) at amino acid position 79 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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0068

T;T;.;.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.53

.;T;.;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.067

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.29

N;N;N;.;N;N

REVEL

Benign

0.021

Sift

Benign

0.16

T;T;T;.;T;T

Sift4G

Benign

0.17

T;T;T;T;T;.

Polyphen

0.0030

B;B;.;.;B;.

Vest4

0.10

MutPred

0.32

Loss of catalytic residue at P79 (P = 0.0322);Loss of catalytic residue at P79 (P = 0.0322);Loss of catalytic residue at P79 (P = 0.0322);Loss of catalytic residue at P79 (P = 0.0322);Loss of catalytic residue at P79 (P = 0.0322);Loss of catalytic residue at P79 (P = 0.0322);

MVP

0.11

MPC

0.21

ClinPred

0.049

GERP RS

1.3

Varity_R

0.029

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over