15-51737469-A-G

Position:

• chr15-51737469-A-G

Variant summary

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

The NM_153374.3(LYSMD2):​c.154T>C​(p.Tyr52His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3	c.154T>C	p.Tyr52His	missense_variant	1/3	ENST00000267838.7	NP_699205.1
LYSMD2	NM_001143917.2	c.1-12348T>C		intron_variant			NP_001137389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD2	ENST00000267838.7	c.154T>C	p.Tyr52His	missense_variant	1/3	1	NM_153374.3	ENSP00000267838	P1
LYSMD2	ENST00000454181.6	c.1-12348T>C		intron_variant		1		ENSP00000410424
LYSMD2	ENST00000558126.1	c.83-12478T>C		intron_variant		5		ENSP00000452715
LYSMD2	ENST00000560491.2	c.-1+371T>C		intron_variant		3		ENSP00000453933

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1271144 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 625398

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Mar 01, 2024

The c.154T>C (p.Y52H) alteration is located in exon 1 (coding exon 1) of the LYSMD2 gene. This alteration results from a T to C substitution at nucleotide position 154, causing the tyrosine (Y) at amino acid position 52 to be replaced by a histidine (H). 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	Pathogenic	1.0
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.97	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.35		Loss of sheet (P = 0.0126);
MVP		0.36
MPC		0.65
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.66
gMVP		0.59

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: chr15-52029666;