Variant chr15-51737429-C-A 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.194G>T(p.Gly65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 1,438,984 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

LYSMD2
NM_153374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.790

Variant links:

Genes affected

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

LYSMD2 links:

Genome browser will be placed here

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=0.091216505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD2	NM_153374.3 linkuse as main transcript	c.194G>T	p.Gly65Val	missense_variant	1/3	ENST00000267838.7	NP_699205.1	Q8IV50-1
LYSMD2	NM_001143917.2 linkuse as main transcript	c.1-12308G>T		intron_variant			NP_001137389.1	Q8IV50-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYSMD2	ENST00000267838.7 linkuse as main transcript	c.194G>T	p.Gly65Val	missense_variant	1/3	1	NM_153374.3	ENSP00000267838.3	Q8IV50-1
LYSMD2	ENST00000454181.6 linkuse as main transcript	c.1-12308G>T		intron_variant		1		ENSP00000410424.2	Q8IV50-2
LYSMD2	ENST00000560491.2 linkuse as main transcript	c.-1+411G>T		intron_variant		3		ENSP00000453933.1	Q8IV50-2
LYSMD2	ENST00000558126.1 linkuse as main transcript	c.83-12438G>T		intron_variant		5		ENSP00000452715.1	H0YK98

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000114

AC:

AN:

61312

Hom.:

AF XY:

0.000167

AC XY:

AN XY:

35906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000577

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1287206

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

634116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000457

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000678

Gnomad4 OTH exome

AF:

0.0000757

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000481

Bravo

AF:

0.0000680

ExAC

AF:

0.0000402

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

Nov 03, 2023

The c.194G>T (p.G65V) alteration is located in exon 1 (coding exon 1) of the LYSMD2 gene. This alteration results from a G to T substitution at nucleotide position 194, causing the glycine (G) at amino acid position 65 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.013

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.49

REVEL

Benign

0.070

Sift

Benign

0.12

Sift4G

Uncertain

0.057

Polyphen

0.0010

Vest4

0.14

MutPred

0.39

Gain of sheet (P = 0.0221);

MVP

0.51

MPC

0.18

ClinPred

0.053

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

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

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