15-51737543-G-A

Position:

• chr15-51737543-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.80C>T​(p.Pro27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000926 in 1,079,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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=0.13587639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3	c.80C>T	p.Pro27Leu	missense_variant	1/3	ENST00000267838.7	NP_699205.1
LYSMD2	NM_001143917.2	c.1-12422C>T		intron_variant			NP_001137389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD2	ENST00000267838.7	c.80C>T	p.Pro27Leu	missense_variant	1/3	1	NM_153374.3	ENSP00000267838.3
LYSMD2	ENST00000454181.6	c.1-12422C>T		intron_variant		1		ENSP00000410424.2
LYSMD2	ENST00000560491.2	c.-1+297C>T		intron_variant		3		ENSP00000453933.1
LYSMD2	ENST00000558126.1	c.83-12552C>T		intron_variant		5		ENSP00000452715.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1079990 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 513444

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000397

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Oct 03, 2022

The c.80C>T (p.P27L) alteration is located in exon 1 (coding exon 1) of the LYSMD2 gene. This alteration results from a C to T substitution at nucleotide position 80, causing the proline (P) at amino acid position 27 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.030
Sift	Benign	0.060	T
Sift4G	Uncertain	0.010	D
Polyphen		0.0040	B
Vest4		0.18
MutPred		0.21		Loss of glycosylation at P27 (P = 0.0071);
MVP		0.17
MPC		0.42
ClinPred		0.74	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.060
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs1359402082; hg19: chr15-52029740; COSMIC: COSV105087118;