chr15-51737441-G-A

Position:

• chr15-51737441-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153374.3(LYSMD2):​c.182C>T​(p.Pro61Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000039 in 1,280,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3823274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3	c.182C>T	p.Pro61Leu	missense_variant	1/3	ENST00000267838.7	NP_699205.1
LYSMD2	NM_001143917.2	c.1-12320C>T		intron_variant			NP_001137389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD2	ENST00000267838.7	c.182C>T	p.Pro61Leu	missense_variant	1/3	1	NM_153374.3	ENSP00000267838.3
LYSMD2	ENST00000454181.6	c.1-12320C>T		intron_variant		1		ENSP00000410424.2
LYSMD2	ENST00000560491.2	c.-1+399C>T		intron_variant		3		ENSP00000453933.1
LYSMD2	ENST00000558126.1	c.83-12450C>T		intron_variant		5		ENSP00000452715.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000390 AC: 5 AN: 1280608 Hom.: 0 Cov.: 33 AF XY: 0.00000476 AC XY: 3 AN XY: 630564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000184

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: 0.00000756

ExAC AF: 0.0000297 AC: 2

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

Nov 18, 2022

The c.182C>T (p.P61L) 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 182, causing the proline (P) at amino acid position 61 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	0.33
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.20
MutPred		0.49		Loss of sheet (P = 0.0084);
MVP		0.50
MPC		0.53
ClinPred		0.99	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.68

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: rs762505010; hg19: chr15-52029638;