2-99292636-C-G

Position:

• chr2-99292636-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174898.3(LYG1):​c.48G>C​(p.Leu16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYG1 NM_174898.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.259

Genes affected

LYG1 (HGNC:27014): (lysozyme g1) Predicted to enable lysozyme activity. Predicted to be involved in defense response to Gram-positive bacterium. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000241962 (HGNC:):

ACMG classification

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=0.05577138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYG1	NM_174898.3	c.48G>C	p.Leu16Phe	missense_variant	4/7	ENST00000308528.9	NP_777558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYG1	ENST00000308528.9	c.48G>C	p.Leu16Phe	missense_variant	4/7	1	NM_174898.3	ENSP00000311320.4
LYG1	ENST00000409448.1	c.48G>C	p.Leu16Phe	missense_variant	5/8	1		ENSP00000386923.1
ENSG00000241962	ENST00000424491.5	n.*293-28490C>G		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460164 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726580

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Apr 06, 2023

The c.48G>C (p.L16F) alteration is located in exon 4 (coding exon 2) of the LYG1 gene. This alteration results from a G to C substitution at nucleotide position 48, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). 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	0.065
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.3
DANN	Benign	0.57
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.28	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;N
REVEL	Benign	0.031
Sift	Benign	0.49	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.73	P;P
Vest4		0.093
MutPred		0.18		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.067
MPC		0.092
ClinPred		0.15	T
GERP RS		-2.8
Varity_R		0.030
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs2094123261; hg19: chr2-99909099;