15-51724923-G-A

Position:

• chr15-51724923-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.472C>T​(p.Pro158Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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=0.07372296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3	c.472C>T	p.Pro158Ser	missense_variant	2/3	ENST00000267838.7	NP_699205.1
LYSMD2	NM_001143917.2	c.199C>T	p.Pro67Ser	missense_variant	2/3		NP_001137389.1
LYSMD2	NM_001363969.2	c.199C>T	p.Pro67Ser	missense_variant	2/3		NP_001350898.1
LYSMD2	XM_047432340.1	c.241C>T	p.Pro81Ser	missense_variant	2/3		XP_047288296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD2	ENST00000267838.7	c.472C>T	p.Pro158Ser	missense_variant	2/3	1	NM_153374.3	ENSP00000267838.3
LYSMD2	ENST00000454181.6	c.199C>T	p.Pro67Ser	missense_variant	2/3	1		ENSP00000410424.2
LYSMD2	ENST00000560491.2	c.199C>T	p.Pro67Ser	missense_variant	2/3	3		ENSP00000453933.1
LYSMD2	ENST00000558126.1	c.151C>T	p.Pro51Ser	missense_variant	2/3	5		ENSP00000452715.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 20, 2023

The c.472C>T (p.P158S) 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 472, causing the proline (P) at amino acid position 158 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	0.062
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.9
DANN	Benign	0.90
DEOGEN2	Benign	0.0014	T;.;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T;.;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.074	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.33	N;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.27	N;N;N;D
REVEL	Benign	0.024
Sift	Benign	0.81	T;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.076	B;.;.;.
Vest4		0.067
MutPred		0.32		Loss of catalytic residue at P158 (P = 0.0064);.;.;.;
MVP		0.38
MPC		0.13
ClinPred		0.092	T
GERP RS		2.5
Varity_R		0.042
gMVP		0.22

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: chr15-52017120;