15-51724892-G-A

Position:

• chr15-51724892-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153374.3(LYSMD2):​c.503C>T​(p.Pro168Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

Genes affected

LYSMD2 (HGNC:28571): (LysM domain containing 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17417571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3	c.503C>T	p.Pro168Leu	missense_variant	2/3	ENST00000267838.7	NP_699205.1
LYSMD2	NM_001143917.2	c.230C>T	p.Pro77Leu	missense_variant	2/3		NP_001137389.1
LYSMD2	NM_001363969.2	c.230C>T	p.Pro77Leu	missense_variant	2/3		NP_001350898.1
LYSMD2	XM_047432340.1	c.272C>T	p.Pro91Leu	missense_variant	2/3		XP_047288296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD2	ENST00000267838.7	c.503C>T	p.Pro168Leu	missense_variant	2/3	1	NM_153374.3	ENSP00000267838.3
LYSMD2	ENST00000454181.6	c.230C>T	p.Pro77Leu	missense_variant	2/3	1		ENSP00000410424.2
LYSMD2	ENST00000560491.2	c.230C>T	p.Pro77Leu	missense_variant	2/3	3		ENSP00000453933.1
LYSMD2	ENST00000558126.1	c.182C>T	p.Pro61Leu	missense_variant	2/3	5		ENSP00000452715.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461806 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727206

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.: 33

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

Dec 27, 2022

The c.503C>T (p.P168L) alteration is located in exon 2 (coding exon 2) of the LYSMD2 gene. This alteration results from a C to T substitution at nucleotide position 503, causing the proline (P) at amino acid position 168 to be replaced by a leucine (L). 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	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	T;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.018
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.086
Sift	Benign	0.063	T;D;D;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.033	B;.;.;.
Vest4		0.17
MutPred		0.29		Gain of stability (P = 0.0417);.;.;.;
MVP		0.60
MPC		0.14
ClinPred		0.77	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-52017089;