Variant 15-51725003-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153374.3(LYSMD2):c.392T>C(p.Ile131Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LYSMD2
NM_153374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

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

LYSMD2 links:

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ACMG classification

Classification made for transcript

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=0.07992637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3 linkuse as main transcript	c.392T>C	p.Ile131Thr	missense_variant	2/3	ENST00000267838.7	NP_699205.1	Q8IV50-1
LYSMD2	NM_001143917.2 linkuse as main transcript	c.119T>C	p.Ile40Thr	missense_variant	2/3		NP_001137389.1	Q8IV50-2
LYSMD2	NM_001363969.2 linkuse as main transcript	c.119T>C	p.Ile40Thr	missense_variant	2/3		NP_001350898.1
LYSMD2	XM_047432340.1 linkuse as main transcript	c.161T>C	p.Ile54Thr	missense_variant	2/3		XP_047288296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYSMD2	ENST00000267838.7 linkuse as main transcript	c.392T>C	p.Ile131Thr	missense_variant	2/3	1	NM_153374.3	ENSP00000267838.3	Q8IV50-1
LYSMD2	ENST00000454181.6 linkuse as main transcript	c.119T>C	p.Ile40Thr	missense_variant	2/3	1		ENSP00000410424.2	Q8IV50-2
LYSMD2	ENST00000560491.2 linkuse as main transcript	c.119T>C	p.Ile40Thr	missense_variant	2/3	3		ENSP00000453933.1	Q8IV50-2
LYSMD2	ENST00000558126.1 linkuse as main transcript	c.83-12T>C		intron_variant		5		ENSP00000452715.1	H0YK98

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251402

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727214

show subpopulations

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000523

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.392T>C (p.I131T) alteration is located in exon 2 (coding exon 2) of the LYSMD2 gene. This alteration results from a T to C substitution at nucleotide position 392, causing the isoleucine (I) at amino acid position 131 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0034

T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.050

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.26

B;.;.

Vest4

0.046

MVP

0.26

MPC

0.16

ClinPred

0.18

GERP RS

1.9

Varity_R

0.058

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over